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Sheep Pulmonary Adenomatosis: Characterization of Two Pathological Forms Associated with Jaagsiekte Retrovirus
Abstract
Pathological and immunohistochemical studies were performed on the lungs of 10 sheep with lesions of "classical" sheep pulmonary adenomatosis (SPA) and six sheep with "atypical" lung tumours. Lung tumour samples and other tissues from the same 16 animals were tested for the presence of jaagsiekte retrovirus (JSRV) by a polymerase chain reaction (PCR) that amplified a portion of the U3 long terminal repeat. The differences in the gross appearance of the classical and atypical forms paralleled the histopathological differences. The latter mainly concerned the stroma of the tumours which in the atypical cases was more heavily infiltrated by inflammatory cells and connective tissue fibres. JSRV major capsid protein was detected immunohistochemically in the epithelial transformed cells of both classical and atypical tumours, but the immune reactivity was slightly milder in atypical SPA. Proviral U3 sequences of JSRV were detected by specific PCR in all the tumour samples. Furthermore, the sequences of amplimers obtained from the two different pathological forms of the tumour were very similar. However, the dissemination of JSRV to other organs was greater in sheep with classical SPA than in those with atypical SPA. The pathological and virological features of these two forms of tumour are compared in an attempt to clarify whether classical and atypical SPA are two separate diseases or different expressions of a single disease spectrum.
... In Europe, the classical OPA has been reported in several countries, such as Ireland, UK, Scotland, Italy, Germany and Spain. The incidence of OPA is usually low, but in some locations it reaches up to 30% and mortality is >50%, causing important economic losses 45 . It can cause about 80% loss of flock for first exposure and 20% for endemic area 2 . ...
... Due to the restricted tumour development in atypical OPA and the lack of overproduction of lung fluid, the atypical form of OPA occurs only as a subclinical finding in abattoir studies or when the animal is necropsied for unrelated reasons. Lesions consist of hard nodules, pearly-white that have a dry cut surface; the tumors are well-delimited by the surrounding pulmonary tissue 3,22,45 . However, nodules resembling atypical lesions have been noted in the same lungs in which the classical form of the tumour is present. ...
... Therefore, these two forms of OPA appear to represent two extremes of a spectrum of histological presentations in this disease 3 . No molecular differences have been found between JSRV associated with these two forms which may represent two extremes of the OPA disease spectrum rather than two separate forms, and atypical OPA might constitute the initial lesions of this spectrum 43,45 . ...
Ovine pulmonary adenocarcinoma (OPA) / Jaagsiekte (Afrikaans: Jaag: Chasing, Driving; Siekte: Sickness - because affected sheep have the appearance of having being chased and the disease is most noticeable when sheep are being herded), earlier known as ovine pulmonary adenomatosis/ovine pulmonary carcinoma. OPA, a progressive respiratory disease, principally affecting adult animals, is a transmissible contagious tumour of lung, brocnchoalveolar carcinoma, caused by exogenous beta retrovirus which has an oncogenic protein that develops lung tumor in sheep and rarely, of goats and moufflons OPA was first described early 19th century in South Africa. OPA was first reported from India in Tamil Nadu State in 1960.
... The atypical type of OPA is less common than the classical version and less contagious. It has been mostly described in Spain, Peru, Iran, and India (Garcia-Goti et al. 2000;Azizi et al. 2014;Mishra et al. 2021). In endemic countries, the mortality rate ranges between 1-5%. ...
... This fluid also accumulates in the upper trachea and discharges from the nostrils. All these lesions represent a classical type of OPA (Garcia-Goti et al. 2000). A single or more white, spherical, tiny nodule of 3-5cm, buried in the diaphragmatic lobe may represent the appearance of a lung tumor in some OPA cases. ...
... De las Heras et al. 1992). Enlargement and edema of mediastinal lymph nodes with or without metastatic tumor lesions are consistent with both forms of OPA(Garcia-Goti et al. 2000).Based on histomorphological lung lesions, OPA were classified into two distinct pathological forms: classical and atypical(Garcia-Goti et al. 2000;De Las Heras et al. 2003;Mishra et al. 2021). In classical form, the affected lung parenchyma shows mixed adenocarcinoma with papillary and acinar growth patterns with alveolar epithelial cells converted to cuboidal or columnar cells. ...
Ovine pulmonary adenocarcinoma (OPA) is a spontaneous lung tumor in sheep caused by Jaagsiekte sheep retrovirus (JSRV) belonging to the Retroviridae. The primary aim of this review work is to give brief insights into the epidemiological aspects of OPA based on a meta-analysis of available research work. This review article also discussed pathogenesis, diagnostic tests and control strategies available for OPA in Sheep. This will help in developing future strategies for disease-free status in India. This disease is endemic in Europe, Africa, Asia, and American continents, causing significant economic losses due to chronic respiratory illness and persistent infections in flocks. The virus is unique among retroviruses with selective affinity to lungs and is the only virus known to cause spontaneous lung tumors in sheep. The incubation time ranges for sheep with naturally occurring OPA ranged from one to four years. There are two pathological forms of the disease: classical and atypical. At an early stage, OPA is difficult to detect in sheep due to a lack of preclinical diagnostic methods, as JSRV is poorly immunogenic and doesn't induce an immune response. PCR, histopathology, and immunohistochemistry are recommended methods for OIE diagnosis. To become a JSRV-free country, mandatory surveillance, detection, and removal of positive animals are required, as OPA is difficult to control due to a lack of vaccines and preclinical diagnostic tests. Due to its similar histological and molecular pathogenesis to that of human lung cancer, OPA is considered an ideal large animal model of human lung adenocarcinoma.
... Grossly, two different forms of OPA are known to occur, the classical and the atypical, although mixed or intermediate forms of OPA have also been cited [6,10]. In the classical form of OPA, the lungs fail to collapse when the thorax is initially opened, and the cranioventral lung is typically the most severely affected [3]. ...
... Affected lungs are heavy, and may exude clear fluid on sectioning; additional frothy fluid may be present in the bronchi and trachea, and concurrent pneumonia is often present [4]. The atypical form of OPA features well-demarcated, solitary, or multifocal nodules, distributed primarily in the caudal pulmonary lobes [3,10]. The neoplastic foci in the atypical form of OPA are more solid than in the classical form, and tend to exude less fluid [4,10]. ...
... The atypical form of OPA features well-demarcated, solitary, or multifocal nodules, distributed primarily in the caudal pulmonary lobes [3,10]. The neoplastic foci in the atypical form of OPA are more solid than in the classical form, and tend to exude less fluid [4,10]. Histologically, OPA lesions are consistent with a well-differentiated, multicentric, bronchioloalveolar carcinoma (adenocarcinoma) [4]. ...
Simple Summary
This paper describes pathological findings in small ruminants with ovine pulmonary adenocarcinoma, a contagious respiratory tumor caused by the jaagsiekte sheep retrovirus. Infection with JSRV leads to the formation of lung tumors, progressive respiratory failure and, ultimately, the death or culling of the affected animals. OPA has traditionally been divided into two forms: classical and atypical. However, in this study, we examined 27 animals with OPA, and found that most of the observed tumors displayed a mix of characteristics from both the classical and the atypical form, and were classified as mixed. Grossly, the lesions were found mostly in the cranial lobes of the lungs, appearing as firm, flat-to-slightly-raised masses that varied in size and color. Histologically, the cases were categorized based on the predominant architectural patterns, with the mixed pattern being the most common. The objective of this study was to provide a detailed description of the gross and microscopic spectrum of ovine pulmonary adenocarcinoma in small ruminants from Spain, focusing on the mixed form. It is important to note that the mixed form of OPA is less frequently reported, and can be mistaken for other concurrent lung diseases.
Abstract
Ovine pulmonary adenocarcinoma (OPA) is a contagious respiratory tumor of small ruminants, manifesting in chronic weight loss and respiratory failure. Infection with the betaretrovirus jaagsiekte sheep retrovirus (JSRV) is the cause of OPA. Here, we describe the gross and microscopic features of twenty-six sheep and one goat with naturally occurring JSRV-associated OPA. All the animals included in this study had pulmonary lesions morphologically consistent with OPA, but the majority of the observed lesions demonstrated features of both the classical and the atypical form of OPA, and were, therefore, classified grossly as mixed. The gross lesions were located mainly in the cranial pulmonary lobes, were multifocal to coalescing, variable in number and size, flat to slightly raised, firm, and white to grey. Histologically, the cases were classified according to the predominant architectural patterns as lepidic, papillary, acinar, or mixed; the mixed histological pattern was the most prevalent. The aim of this study was to describe the gross and microscopic spectrum of OPA in naturally infected small ruminants from Spain. The mixed form of OPA is less commonly reported, and can be confused with other concurrent pulmonary pathologies (such as BALT hyperplasia in SRLV-associated pneumonia or lungworm granulomas).
... The two types may coexist in the same exploration and in the same animal, along with intermediate forms [9,52,53]. In the classic form, which is the most frequent, neoplastic lesions diffusely affect the cranioventral areas of the lung, although any other area may be involved [22,54,55]. The lungs are increased in volume and weight, up to 3 to 4 times, and fail to collapse, during the opening of the chest cavity [22]. ...
... The consistency of tumor areas is increased, with a narrow band of pulmonary emphysema surrounding them, and the slight pressure causes clear, cloudy, foamy fluid arising from the bronchioles and bronchi. In advanced cases, the affected areas have a lardaceous, whitish, hard and solid appearance as a result of fibrosis [22,[54][55][56]. ...
... In early cases, when clinical signs are not evident, the lesions may be confined to a very restricted pulmonary area, including in the form of a single tumor nodule, with very small dimensions [54]. The pleura is sometimes affected, with fibrosis and adhesions between the parietal and visceral surfaces, particularly at the anterior lobes [22]. ...
Ovine pulmonary adenocarcinoma (OPA), also known as sheep pulmonary adenomatosis and jaagsiekte, is a contagious pulmonary tumor of sheep, characterized by neoplastic proliferation of type II pneumocyte and club cells. OPA is induced by the oncogenic activity of the envelope glycoprotein (Env) of exogenous jaagsiekte sheep retrovirus (JSRV). This disease is associated with significant economic losses in numerous sheep raising countries. The onset of suggestive clinical signs is often late, making difficult the early diagnosis of the disease and timely implementation of control measures on the affected farms. Further, the lack of diagnostic tests that can be performed routinely by veterinary clinicians to accurately assess infected animals (e.g., serological or others) means that the true prevalence at flock level is not known. Imaging diagnostic methods (e.g., ultrasound, X-ray and computed tomography) can be used to support the clinical diagnosis, even in pre-clinical stages in affected flocks. The diagnosis must be confirmed by PCR of nasal excretions or immunohistochemistry and PCR of tumor lesions. No vaccine for OPA has yet been developed. Thus, in this work, we review the main methods of diagnosis of OPA in order to support the clinician in the identification of the disease, avoid underdiagnosis and allow the implementation of suitable measures to prevent and control its spread.
... The etiological agent of OPA is exogenous Jaagsiekte Sheep Retrovirus (exJSRV). A specific U3 long terminal repeat (LTR) sequence of exJSRV was detected in lungs from affected animals [3,4]. The LTR region varies among different retroviruses, including JSRV [5], sheep endogenous retrovirus [3] and ovine enzootic nasal tumour virus [6]. ...
... There are two recognized forms of OPA which show gross, histological and immunohistochemical differences [4,12,16]. The lesions in classical OPA predominantly affect all pulmonary lobes and are located in the cranioventral area. ...
... More than 50% of the affected animals usually die because of progressive respiratory failure [24], therefore causing important economic losses. The atypical OPA is less contagious than classical form [4]. The atypical OPA has been reported in Spain, Peru, Iran and India [4,12,16,25], but there is no evidence of its occurrence in other countries where OPA is commonly found. ...
Background:
Ovine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus (exJSRV). The prevalence of JSRV-related OPA in Eastern European countries, including Romania is unknown. We aimed to investigate: the prevalence and morphological features of OPA (classical and atypical forms) in the Transylvania region (Romania), the immunophenotype of the pulmonary tumors and their relationships with exJSRV infection. A total of 2693 adult ewes slaughtered between 2017 and 2019 in two private slaughterhouses from Transylvania region (Romania) was evaluated. Lung tumors were subsequently assessed by cytology, histology, immunocytochemistry, immunohistochemistry, electron microscopy and DNA testing.
Results:
Out of 2693 examined sheep, 34 had OPA (1.26% prevalence). The diaphragmatic lobes were the most affected. Grossly, the classical OPA was identified in 88.24% of investigated cases and the atypical OPA in 11.76% that included solitary myxomatous nodules. Histopathology results confirmed the presence of OPA in all suspected cases, which were classified into acinar and papillary types. Myxoid growths (MGs) were diagnosed in 6 classical OPA cases and in 2 cases of atypical form. Lung adenocarcinoma was positive for MCK and TTF-1, and MGs showed immunoreaction for Vimentin, Desmin and SMA; Ki67 expression of classical OPA was higher than atypical OPA and MGs. JSRV-MA was identified by IHC (94.11%) in both epithelial and mesenchymal cells of OPA. Immunocytochemistry and electron microscopy also confirmed the JSRV within the neoplastic cells. ExJSRV was identified by PCR in 97.05% of analyzed samples. Phylogenetic analysis revealed the presence of the exJSRV type 2 (MT809678.1) in Romanian sheep affected by lung cancer and showed a high similarity with the UK strain (AF105220.1).
Conclusions:
In this study, we confirmed for the first time in Romania the presence of exJSRV in naturally occurring OPA in sheep. Additionally, we described the first report of atypical OPA in Romania, and to the best of our knowledge, in Eastern Europe. Finally, we showed that MGs have a myofibroblastic origin.
... The etiological agent of OPA is exogenous Jaagsiekte Sheep Retrovirus (exJSRV). A specific U3 long terminal repeat (LTR) sequence of exJSRV was detected in lungs from affected animals [3,4]. The LTR region varies among different retroviruses, including JSRV [5], sheep endogenous retrovirus [3] and ovine enzootic nasal tumour virus [6]. ...
... There are two recognized forms of OPA which show gross, histological and immunohistochemical differences [4,12,16]. The lesions in classical OPA predominantly affect all pulmonary lobes and are located in the cranioventral area. ...
... More than 50% of the affected animals usually die because of progressive respiratory failure [24], therefore causing important economic losses. The atypical OPA is less contagious than classical form [4]. The atypical OPA has been reported in Spain, Peru, Iran and India [4,12,16,25], but there is no evidence of its occurrence in other countries where OPA is commonly found. ...
... Inclement weather and physiological state of animals often contribute to onset and progression of pneumonias, wherein bacterial as well as viral infections are combined (Lacasta et al. 2008). Ovine pulmonary adenocarcinoma (OPA), also known as jaagsiekte or sheep pulmonary adenomatosis, is a transmissible lung cancer caused by the jaagsiekte sheep retrovirus (JSRV), a member of the genus Betaretroviruses of the family Retroviridae (Palmarini et al. 1999;Garcia-Goti et al. 2000;Sharp and DeMartini 2003). OPA has a global impact, except for Australia and New Zealand, and has been eradicated from Iceland (De las Heras et al. 2014). ...
... On the basis of gross and histopathology, some of the affected lungs analyzed in this study showed grayish to purple color, satellite tumor nodules with moist surface, and airways filled with copious fluid, which are in concurrence with the classical form of OPA (Garcia-Goti et al. 2000), while some affected lungs showed an atypical form (i.e. a solitary tumor nodule in the diaphragmatic lobe and several smaller nodules in the main lobes, with hard, pearly white, and dry cut surface), which are in accordance with observations of previous reports (Palmarini et al. 1996;Devi et al. 2014). A mix of both characteristics was also observed by De las Heras et al. (2010). ...
... The detection of OPA-causing provirus in clinical samples such as blood and bronchoalveolar lavage (BAL), among others, from live animals or lung tumor samples from abattoir cases by PCR is useful for the identification of infected sheep. This technique may be useful for control or eradication programs and had been successfully employed in a lot of studies for diagnosis of OPA (Garcia-Goti et al. 2000;Voigt et al. 2007, Lewis et al. 2011). In the present study, U3 and gag-specific PCR products confirmed the presence of JSRV proviral DNA in 31 infected lung samples of sheep. ...
... Inclement weather and physiological state of animals often contribute to onset and progression of pneumonias, wherein bacterial as well as viral infections are combined (Lacasta et al. 2008). Ovine pulmonary adenocarcinoma (OPA), also known as jaagsiekte or sheep pulmonary adenomatosis, is a transmissible lung cancer caused by the jaagsiekte sheep retrovirus (JSRV), a member of the genus Betaretroviruses of the family Retroviridae (Palmarini et al. 1999;Garcia-Goti et al. 2000;Sharp and DeMartini 2003). OPA has a global impact, except for Australia and New Zealand, and has been eradicated from Iceland (De las Heras et al. 2014). ...
... On the basis of gross and histopathology, some of the affected lungs analyzed in this study showed grayish to purple color, satellite tumor nodules with moist surface, and airways filled with copious fluid, which are in concurrence with the classical form of OPA (Garcia-Goti et al. 2000), while some affected lungs showed an atypical form (i.e. a solitary tumor nodule in the diaphragmatic lobe and several smaller nodules in the main lobes, with hard, pearly white, and dry cut surface), which are in accordance with observations of previous reports (Palmarini et al. 1996;Devi et al. 2014). A mix of both characteristics was also observed by De las Heras et al. (2010). ...
... The detection of OPA-causing provirus in clinical samples such as blood and bronchoalveolar lavage (BAL), among others, from live animals or lung tumor samples from abattoir cases by PCR is useful for the identification of infected sheep. This technique may be useful for control or eradication programs and had been successfully employed in a lot of studies for diagnosis of OPA (Garcia-Goti et al. 2000;Voigt et al. 2007, Lewis et al. 2011). In the present study, U3 and gag-specific PCR products confirmed the presence of JSRV proviral DNA in 31 infected lung samples of sheep. ...
An epidemiological study was conducted along with pathological, immunohistochemistry (IHC) of capsid antigen and molecular detection of jaagsiekte sheep retrovirus (JSRV) causing ovine pulmonary adenocarcinoma (OPA) in sheep and goats population from three states of India viz. Delhi, Gannavaram (Andhra Pradesh), and Bareilly (Uttar Pradesh). A total of 1350 lungs samples were screened and out of which 31 (2.29%) animals were found to be positive [sheep (3.49%) and goats (0.00%)] for JSRV. The prevalence of infection was recorded Gannavarum (20.00%) followed by Delhi (2.10%) and no any positive cases found in Bareilly area.
... 6,22 This tumor, which can develop naturally or be experimentally induced, originates from alveolar type II pneumocytes and Clara cells. 8,26 The disease occurs in sheepbreeding areas worldwide, but has been eradicated in Iceland. The economic ramifications of OPA are significant, reportedly leading to losses of up to 80% in herds following first exposure to the virus. ...
... Ovine pulmonary adenocarcinoma is a disease generally seen in sheep aged between 2 and 4 years 8,14 and, in the current study, it was recorded in 3-4-year-old animals. Two forms of OPA, classical and atypical, are known. ...
... Two forms of OPA, classical and atypical, are known. 6,8 Classical lesions are nodular or diffuse, firm, and are seen as graywhite foci that form by the fusion of nodules, particularly in the cranioventral portions of the lobes. The cut surfaces of these foci are wet, and large amounts of frothy exudate are evident in the bronchi and bronchial areas. ...
Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring cancer in sheep that is caused by the Jaagsiekte sheep retrovirus (JSRV). Because the pathological and epidemiological features of OPA are similar to those of bronchoalveolar carcinoma in humans, OPA is considered a useful animal model for pulmonary carcinogenesis. In this study, 3,512 lungs from various breeds of sheep were collected and macroscopically examined. OPA was identified in 30 sheep, and samples of these animals were further examined by histologic, immunohistochemical (p53 protein, surfactant protein A [SP-A], proliferating cell nuclear antigen [PCNA], JSRV matrix protein [MA]), and polymerase chain reaction (PCR) methods. Papillary or acinar adenocarcinomas were detected microscopically in the affected areas. Immunoreactivity for p53 PAb240 was detected in 13 sheep, whereas p53 DO-1 was not detected in any of the OPA animals. PCNA immunoreactivity was recorded in 27 animals. SP-A and JSRV MA protein was immunopositive in all 30. JSRV proviral DNA was detected by PCR analysis in all of the lung samples collected from OPA animals. In addition, the pulmonary SP-A levels were increased in tumor cells. The results of this study suggest that PCNA and p53 protein expression may be useful indicators in monitoring malignancy of pulmonary tumors.
... 6,22 This tumor, which can develop naturally or be experimentally induced, originates from alveolar type II pneumocytes and Clara cells. 8,26 The disease occurs in sheepbreeding areas worldwide, but has been eradicated in Iceland. The economic ramifications of OPA are significant, reportedly leading to losses of up to 80% in herds following first exposure to the virus. ...
... Ovine pulmonary adenocarcinoma is a disease generally seen in sheep aged between 2 and 4 years 8,14 and, in the current study, it was recorded in 3-4-year-old animals. Two forms of OPA, classical and atypical, are known. ...
... Two forms of OPA, classical and atypical, are known. 6,8 Classical lesions are nodular or diffuse, firm, and are seen as graywhite foci that form by the fusion of nodules, particularly in the cranioventral portions of the lobes. The cut surfaces of these foci are wet, and large amounts of frothy exudate are evident in the bronchi and bronchial areas. ...
Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring cancer in sheep that is caused by the Jaagsiekte sheep retrovirus (JSRV). Because the pathological and epidemiological features of OPA are similar to those of bronchoalveolar carcinoma in humans, OPA is considered a useful animal model for pulmonary carcinogenesis. In this study, 3,512 lungs from various breeds of sheep were collected and macroscopically examined. OPA was identified in 30 sheep, and samples of these animals were further examined by histologic, immunohistochemical (p53 protein, surfactant protein A [SP-A], proliferating cell nuclear antigen [PCNA], JSRV matrix protein [MA]), and polymerase chain reaction (PCR) methods. Papillary or acinar adenocarcinomas were detected microscopically in the affected areas. Immunoreactivity for p53 PAb240 was detected in 13 sheep, whereas p53 DO-1 was not detected in any of the OPA animals. PCNA immunoreactivity was recorded in 27 animals. SP-A and JSRV MA protein was immunopositive in all 30. JSRV proviral DNA was detected by PCR analysis in all of the lung samples collected from OPA animals. In addition, the pulmonary SP-A levels were increased in tumor cells. The results of this study suggest that PCNA and p53 protein expression may be useful indicators in monitoring malignancy of pulmonary tumors.
... The pathognomonic feature of OPA was the accumulation of lung fluid within the respiratory tract, which may flow from the nostrils when the hind quarters were raised [20]. In the present study, all the OPA sheep showed mucus discharges from the nostrils that was more abundant in sheep No. 5. Grossly, diffuse consolidated areas or discrete nodules seen in the affected lungs with moist surfaces were similar to that of classical form of OPA [1] [19] [23]- [25]. There are descriptions of classical and atypical forms of OPA in the literature [23]- [25]. ...
... In the present study, all the OPA sheep showed mucus discharges from the nostrils that was more abundant in sheep No. 5. Grossly, diffuse consolidated areas or discrete nodules seen in the affected lungs with moist surfaces were similar to that of classical form of OPA [1] [19] [23]- [25]. There are descriptions of classical and atypical forms of OPA in the literature [23]- [25]. Three anatomical forms consisting of grey nodules with moist surface in classical form, white, dry and firm nodules clearly demarcated, either solitary or multiple in atypical form and both characteristics in mixed form were described in lungs for the first time by De Las Heras et al. [24] Later, the classical form of OPA characterized by a firm, greyish to purple neoplastic mass often surrounded by satellite tumor nodules with the cut section of tumor mass invariably having a wet appearance and copious fluid filling the airways and the atypical form showing a solitary tumor nodule in the diaphragmatic lobe and several smaller nodules in the main lobes, with hard and pearly white and a dry cut surface were reported [25]. ...
... There are descriptions of classical and atypical forms of OPA in the literature [23]- [25]. Three anatomical forms consisting of grey nodules with moist surface in classical form, white, dry and firm nodules clearly demarcated, either solitary or multiple in atypical form and both characteristics in mixed form were described in lungs for the first time by De Las Heras et al. [24] Later, the classical form of OPA characterized by a firm, greyish to purple neoplastic mass often surrounded by satellite tumor nodules with the cut section of tumor mass invariably having a wet appearance and copious fluid filling the airways and the atypical form showing a solitary tumor nodule in the diaphragmatic lobe and several smaller nodules in the main lobes, with hard and pearly white and a dry cut surface were reported [25]. On histological examination, the lung sections from consolidated areas or tumor nodules revealed proliferation of alveolar or bronchiolar epithelial cells giving either papillary or acinar pattern. ...
... Tumor distribution in this case was dorsal, not cranioventral, as reported in the literature. The pulmonary changes in OPA can be grouped into two morphologic patterns, namely "classical" and "atypical" (20) . The classical OPA tends to be locally extensive, has a cranioventral distribution and on the cut-surface oozes clear fluid. ...
... Lepidic growth relates to proliferating neoplastic cells along the intact surface of alveolar walls without vascular stromal or vascular invasion (12,15) . In this case, the prevailing growth patterns were lepidic and papillary types, which are the most commonly seen in OPA (3,20) . ...
Ovine pulmonary adenocarcinoma is a transmissible pulmonary malignancy of sheep caused by a beta-retrovirus currently named Jaagsiekte sheep retrovirus (JSRV). Club cells (formerly Clara cells) in the bronchiole and type II pneumonocytes in the alveoli are the target oncogenic cells for this virus. Characterized clinically by intermittent cough, abundant nasal discharge, and progressive weight loss, the tumors randomly involve all lung lobes or have a cranioventral distribution mimicking bronchopneumonia. The definitive diagnosis of ovine pulmonary adenocarcinoma requires identifying Jaagsiekte sheep retrovirus or associated specific proteins in neoplastic cells such as JSRV-Env oncogenic protein. A two-year-old Male Pelibuey sheep with a history of chronic cough and progressive weight loss was treated unsuccessfully with antibiotics and died a few days later. Postmortem examination revealed lung edema and several nodular to locally extensive masses in the lungs. Microscopically the tumoral tissues were composed of clusters of neoplastic epithelial cells exhibiting a lepidic growth pattern typical of pulmonary carcinoma. Tumoral cells were immunopositive for Jaagsiekte sheep retrovirus-Env oncogenic protein. Based on these findings, the final diagnosis of ovine pulmonary adenocarcinoma was made.
... Ovine pulmonary adenomatosis (OPA) also known as Jaagsiektediseae, or pulmonary adenocarcinoma and its chronic respiratory disease of sheep or contagious lung cancer of sheep, and less common in goats. The disease is caused by a virus called Jaagsiekte sheep betaretrovirus (JSRV) belonging to the Retroviridae family, Orthoretrovirinae subfamily and genus Betaretrovirus genus [1], [2]. The disease occurs either naturally or by experimentally induced, generated either from alveolar epithelial cells type II pneumocytes or clara cells. ...
... Researchers found that the occurrence of cancers in respiratory systems including lung cancers in animals compared to lung cancers of humans have a lower incidence as well as compared with other systems. In contrast, the lung is regarded as an important organ for transferring of tumor as metastasis in animals and humans [2]. In sheep, OPA found the most famous cancer involving of the respiratory [27]. ...
Ovine Pulmonary Adenomatosis is a chronic respiratory disease of sheep or contagious lung cancer of sheep, and less commonly of goats. A total of 4061 lung samples were selected randomly from slaughtered sheep and goats. All samples of lungs with typical lesions were fixed in 10% neutral buffered formalin and examination is performed by macrocsopical and microscopical observation. To perform IHC technique, we used TMA with a polymer system by application of specific markers Napsin A. Results showed 35 lungs suspected from natural cases are diagnosed as OPA. Histologically results showed that the presence of multiple proliferations foci of neoplastic cells in the epithelial cell of alveoli and bronchi, these proliferations appears either papillary or as impression of solid growths appearance or acinar shape which is classified as classical and atypical form. The current study found that the expression of Nnapsin A was observed in 85.71% of the OPA as a granular cytoplasmic staining but there was staining in the nucleus of tumor cells. In conclusion, these findings indicate for the first time that Napsin A is extremely specific for adenocarcinoma of lung in primary origin and use of this important biomarker is guaranteed to help disconnect primary pulmonary adenocarcinoma for diagnosis from other types of lung cancer.
... In classical forms, neoplastic lesions occur mainly in the central cranial parts of all lobes of the lung. Atypical forms tend to be more nodular in both early and advanced tumours [21]. ...
... In contrast, there are few reports of atypical OPA. This study reports the atypical OPA as greyishwhite, dried subdural nodules or confluent lesions about 2-3 cm in diameter and some of these lumps were pearly white and dry similarly findings of other researchers [21], [31] . Interestingly, this study showed every form present in deferent lung while some reports showed that both forms are present in the same lung [21,31,[37]. ...
Aims: To determine a first estimate of the prevalence of Ovine Pulmonary Adenocarcinoma (OPA) in slaughtered sheep in East of Libya and to investigate morphopathological characteristics of OPA forms in native sheep of Libya. Study Design: This study was carried out in some El-Beida slaughterhouses (in an eastern part of Libya) during the period from October 2020 to April 2021. Methods: The animal involved in this study was native sheep of more than 4 months age. Lungs of 525 sheep carcasses were examined then full sections (n= 141) were used for histopathological examination. Results: OPA was detected in 1.1% of all examined cases and in 2.97% of affected lungs. 4 out of 6 sheep, showed the classical form whereas atypical lesions were detected in 2 out of 6 sheep. Histopathological changes were almost similar in the two forms of the disease. Conclusion: OPA is well documented for the first time in sheep from El-Beida area and classical and atypical forms of OPA were reported and described. Moreover, this study provides a morphological background necessary for routine differentiation and indicates the necessity for initiating further studies on identifying the epidemiology, etiological agents and pathogenesis of OPA in Libyan sheep
... OPA is a contagious tumour arising from alveolar type II pneumocytes and rarely from non-ciliated bronchiolar (Clara) cells. Tumour metastases can be found in thoracic and occasionally in extrathoracic tissues (6,7,8,22,25). The disease is caused by an exogenous β-retrovirus, known as Jaagsiekte sheep retrovirus (JSRV), which induces oncogenic transformation of alveolar and bronchiolar secretory epithelial cells (21). ...
... OPA occurs naturally in sheep and rarely in goats (21). Although the disease may affect lambs as young as two months old, sheep most often show clinical features at 2-4 years of age (8,12,28). In some affected flocks, the annual mortality rate due to the disease may be as high as 10%-20%, although the rate of 1%-3% is more common (28). ...
In a disaster event involving water, the length of time that collection materials remain wet is a critical factor in determining whether a successful recovery is possible. There is a substantial knowledge base for the water immersion resistance of traditional information carriers such as paper documents but not for electronic storage media. In this study, floppy diskettes, VHS videotapes, optical discs, and flash media, were immersed in different water baths for various time intervals. The baths consisted of two different sources of tap water, a more corrosive tap water solution, and artificial seawater. Most electronic media survived well in clean tap water but problems occurred with some CDs and VHS tapes. More damage became evident with electronic storage media when the immersion bath was more corrosive. For some media, such as optical discs, whether damage occurred was likely linked to the manufacturing quality of the media. Drying methods were also explored. Air-drying was determined to be the best method for recovering wet electronic storage media. Freeze-thaw-air drying and vacuum freeze-drying methods can destroy CDs and DVDs and should be avoided. If wet materials cannot be recovered and dried promptly, it was established that storage in cool water reduces deterioration significantly.
... OPA is a contagious tumour arising from alveolar type II pneumocytes and rarely from non-ciliated bronchiolar (Clara) cells. Tumour metastases can be found in thoracic and occasionally in extrathoracic tissues (6,7,8,22,25). The disease is caused by an exogenous β-retrovirus, known as Jaagsiekte sheep retrovirus (JSRV), which induces oncogenic transformation of alveolar and bronchiolar secretory epithelial cells (21). ...
... OPA occurs naturally in sheep and rarely in goats (21). Although the disease may affect lambs as young as two months old, sheep most often show clinical features at 2-4 years of age (8,12,28). In some affected flocks, the annual mortality rate due to the disease may be as high as 10%-20%, although the rate of 1%-3% is more common (28). ...
Introduction: The aim of this study was to use TaqMan real-time PCR technique to investigate Jaagsiekte sheep retrovirus (JSRV) proviral DNA in whole blood samples of sheep, and compare the results to those of histopathological examinations. Material and Methods: Eighty blood samples from clinically healthy sheep were randomly collected before the animals were slaughtered. Ten tissue samples from each lung and associated caudal mediastinal lymph node were taken. Results: Fifteen (18.75%) blood samples were found to contain proviral DNA, and 11 (13.75%) corresponding lung samples showed microscopic changes consistent with ovine pulmonary adenocarcinoma. None of the samples displayed metastases to the caudal mediastinal lymph nodes. The prominent pattern of neoplastic nodules consisted of acinar (alveolar) form. Conclusion: The results indicated the higher sensitivity of real-time PCR compared to histopathological examinations in detection of ovine pulmonary adenocarcinoma.
... The gross lesions observed in the lungs of adult sheep and microscopic proliferative changes observed in the alveolar and bronchiolar epithelium were consistent with the observations of the previous OPA studies [2,9,22]. There was infiltration of numerous macrophages in the lumen and in the vicinity of proliferated alveoli as previously reported by various workers in both natural and experimentally induced OPA [23,24]. The pathogenic role of macrophages in OPA has not been fully demonstrated, however, it was suggested that these cells may be useful in clearance of excess surfactant secreted by the neoplastic type II pneumocytes. ...
... It was also demonstrated that the tumor cells secrete a chemotactic factor that might be responsible for the recruitment of macrophages [25]. Infiltration of the inflammatory cells particularly neutrophils in the alveoli of affected lungs in present report may reflect secondary bacterial infection [24,26]. Further, OPA affected sheep lack circulating anti-JSRV antibodies and have an increased susceptibility to secondary bacterial infection, indicate that OPA affected sheep are immunocompromised [27]. ...
Aim:
This study was aimed to detect ovine pulmonary adenocarcinoma (OPA) in sheep flocks affected with pulmonary disorders at organized farm.
Materials and methods:
A total of 75 sheep died naturally were thoroughly examined for the lesions of OPA during necropsy. Tissue sections from affected portion of the lungs from each animal were collected aseptically and divided into two parts; one each for polymerase chain reaction (PCR) and another for histopathology.
Results:
On PCR examination of lung tissues, six sheep (8%) were found to be positive for JSRV. Two of them were 3-6 months of age and did not show clinical signs/gross lesions of OPA. Four adult sheep positive on PCR revealed characteristic lesions of OPA on gross and histopathological examination.
Conclusion:
In the absence of known specific antibody response to the infection with JSRV, there is no diagnostic serological test available. The PCR assay employed in this study on lung tissues, using primers based on the U3 region of the viral long terminal repeat for JSRV would be helpful in the screening of preclinical and clinical cases of OPA in sheep.
... Two pathological forms, classical and atypical, of ovine pulmonary adenocarcinoma (pulmonary adenomatosis) have been described. Both are associated with infection by a widely prevalent betaretrovirus, Jaagsiekte sheep retrovirus (García-Goti et al., 2000;De las Heras et al., 2003a;Griffiths et al., 2010). Although mainly a disease of sheep, ithas also been reported in goats (De las Heras et al., 2003a). ...
... In addition, nodular, spiral-shaped proliferations of myxomatous tissue have been reported. The main differences between classical and atypical ovine pulmonary adenocarcinoma is that in the latter, para-adenomatous macrophages are much less abundant while infiltration of the tumour stroma by inflammatory cells and connective tissue is more prominent (García-Goti et al., 2000;De las Heras et al., 2003a). Jaagsiekte sheep retrovirus capsid and envelope proteins can be detected in the neoplastic cells by immunohistochemistry, not only in the affected lung (Griffiths et al., 2010) but also in intra-and extra-thoracic metastases (Minguijón et al., 2013). ...
... The gross lesions observed in the lungs of adult sheep and microscopic proliferative changes observed in the alveolar and bronchiolar epithelium were consistent with the observations of the previous OPA studies [2,9,22]. There was infiltration of numerous macrophages in the lumen and in the vicinity of proliferated alveoli as previously reported by various workers in both natural and experimentally induced OPA [23,24]. The pathogenic role of macrophages in OPA has not been fully demonstrated, however, it was suggested that these cells may be useful in clearance of excess surfactant secreted by the neoplastic type II pneumocytes. ...
... It was also demonstrated that the tumor cells secrete a chemotactic factor that might be responsible for the recruitment of macrophages [25]. Infiltration of the inflammatory cells particularly neutrophils in the alveoli of affected lungs in present report may reflect secondary bacterial infection [24,26]. Further, OPA affected sheep lack circulating anti-JSRV antibodies and have an increased susceptibility to secondary bacterial infection, indicate that OPA affected sheep are immunocompromised [27]. ...
... The current study describes the classical and pathognomic of gross and microscopic lesions caused by natural infection with neoplastic retrovirus in sheep that causes ovine pulmonary adenocarcinomas. The gross lesions were described previously as pale to purple areas of neoplastic tissue present mainly in the cranioventral lobe of the lung, and in severe cases, it includes all lobes of the lungs; these areas were firm in cut and having areas filled with necrotic tissues, also these areas characterized by slightly elevated above the lung surface with red color zone of demarcation, in addition to pinpoint hemorrhages areas may be recorded (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). ...
... The use of PCR to detect OPA-causing proviruses in lung samples from abattoir cases has proven valuable technique for identifying infected sheep and goats. This method has been effectively applied in multiple studies for OPA diagnosis and it can greatly support control and eradication activities 11 . ...
A two-years-old goat with anorexia, progressive emaciation and weak body condition were received for post mortem examination in the Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry, Himmatnagar from Teaching Veterinary Clinical Complex, CVS & AH, Himmatnagar, Gujarat. Grossly, diffuse pale oedematous lungs were found. Mediastinal lymph nodes revealed mild congestion and oedema. Further, PCR was used for molecular detection of jaagsiekte sheep retrovirus (JSRV). The presence of jaagsiekte was confirmed by PCR results with anticipated sizes of 229 bp and 176 bp for the gag gene and U3 region of the JSRV genome, respectively.
... The selection criteria for samples included: (1) all pulmonary masses were grossly classified as the classical form of OPA according to Garcia-Goti et al. (2000) and Toma et al., (2019) [5,58]; (2) all tumors were histologically diagnosed as pulmonary adenocarcinomas without myxoid growths [23,59]; (3) JSRV infection was confirmed in all tumors by immunohistochemistry and PCR [5]; (4) JSRV-negative pulmonary tissues that had no significant histological changes were used as controls. ...
Background
Ovine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV) and is considered an important potential animal model for human lung cancer. The precise mechanisms of OPA oncogenesis are still uncertain. The transcription factor signal transducer and activator of transcription 3 (STAT3) is activated by interleukin-6 (IL-6) in many cancers, but this aspect is unknown in OPA. We therefore aimed to evaluate the expression of IL-6 and STAT3 in OPA for its potential role in pulmonary carcinogenesis.
Results
Lung tissues from 9 grossly normal and JRSV-negative sheep and 20 cases of JSRV-positive OPA sheep were included in the study. Tissue samples were stained with antibodies against IL-6, STAT3, and JSRV-MA. IL-6 and STAT3 were further quantified in both groups using Western Blot (WB). Immunohistochemically, IL‑6 was expressed in stromal, inflammatory, and epithelial cells in all cases of OPA, while STAT3 immunoexpression was restricted to epithelial cells. In the OPA group, the percentage of immunolabelled cells for STAT3 accounted for a mean value of 96%. Using the H-SCORE method, 95% of cases were considered positive for STAT3 expression. Control tissues showed multifocal and weak immunoexpression for both markers. Using WB analyses, a highly significant amount of both IL-6 (p = 0.0078) and STAT3 (p < 0.0001) proteins were present in lung neoplasms, by comparison to the control lungs.
Conclusions
Our data showed overexpression of IL-6 and STAT3 in lung tissues from OPA compared to lungs from JSRV-negative sheep. These results suggest a potential role of IL6-STAT3 in OPA carcinogenesis.
... The disease is classified pathologically into two forms either classical or atypical forms. In the first from classical, the neoplastic foci occurs in the cranioventral area of all lung lobes, while in the second form atypical, tend to be more granular in both early and late tumors [7,8]. Histopathologically, the tumor cells characterized by a papillary or acinar adenocarcinoma, which is appears as cuboidal or columnar cells are lining of bronchi and alveoli, the tumor area are surrounded by a zone of connective tissue which is infiltrated with mononuclear inflammatory cells, while the atypical form the tumor cells appears as solitary or multiple nodules in the lung and usually located in the diaphragmatic lobe, histopathologically tumor cells characterized by same features of classical form except severally infiltrated by mononuclear inflammatory cells and zone of fibrous connective tissue [1,9] Because little information has been carried out OPA in Iraq especially in the Kurdistan region, therefore, our current study was carried out to the study of the prevalence and pathological changes of OPA in sheep and goats at Duhok abattoir in Kurdistan region of Iraq. ...
... Characteristically, the alveoli adjacent to the neoplastic nodules are filled with enlarged, foamy macrophages, which are called paraadenomatous areas. The main histological difference between classical and atypical OPA is that in the latter, the macrophages are much less abundant, while infiltration of the tumor stroma by inflammatory cells and connective tissue is prominent (GARCÍA-GOTI et al., 2000;DE LAS HERAS et al., 2003a). JSRV virions can be visualized in OPA-affected lungs through electronic microscopy (DE LAS HERAS et al., 2003a). ...
The increase in sheep production is directly related to the health status of the flock. Brazil is one of the largest sheep producers in the world, and the sheep flock is concentrated in southern and northeast regions. Infectious diseases are responsible for severe economic losses resulting from a decrease in milk and meat production, deaths, and cost of treatment. Among infectious diseases, viral diseases are described chiefly in case reports or retrospective studies. This study aimed to review the main features of viral diseases that affect sheep in Brazil and their current situation in the Brazilian territory. We included eight viral diseases described in Brazil: rabies, bluetongue, contagious ecthyma, foot and mouth disease, visna-maedi, enzootic nasal tumor, ovine pulmonary adenocarcinoma, and border disease. We review the etiological, epidemiological, clinical, and pathological findings for each agent and included differential diagnoses, information on recommended diagnostic methods to confirm the disease etiology, and control measures. This study served as quick consultation material for field veterinarians for an accurate diagnosis.
... All samples were subdivided and either xed in 10% buffered formalin for microscopical investigations or the tissues were stored at -20°C for molecular tests. [5,23]; 2) all tumors were histologically diagnosed as pulmonary adenocarcinomas without myxoid growths [24,25]; 3) JSRV infection was con rmed in all tumors by immunohistochemistry and PCR [5]; 4) JRSV-negative pulmonary tissues that also had no signi cant histological changes were used as controls. ...
Background
Ovine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV) and is considered the most suitable animal model for human lung cancer. The precise mechanisms of OPA oncogenesis are still uncertain. Signal transducer and activator of transcription 3 (STAT3) is activated by interleukin-6 (IL-6) in many cancers, but this aspect is unknown in OPA. We aimed to evaluate the expression of IL-6 and STAT3 in OPA for its potential role in pulmonary carcinogenesis.
Results
Twenty cases of JSRV-positive OPA and 9 normal lung tissues from sheep were included in the study. Tissue samples were stained with antibodies for IL-6, STAT3, and JSRV-MA. IL-6 and STAT3 were semi-quantified in OPA and control groups using Western Blot (WB). IL‑6 was expressed in stromal, inflammatory, and epithelial cells in all cases of OPA, while STAT3 expression was restricted to epithelial cells. In the OPA group, the percentage of immunolabelled cells for STAT3 accounted for a mean value of 96%. Using the H-SCORE method, 95% of cases were considered positive for STAT3 expression. Control tissuesshowed multifocal andweak immunoexpression for both markers. Using WB analysis, a highly significant amount of both IL-6 (p=0.0078) and STAT3 (p<0.0001) proteins were detected in lung neoplasms compared to controls.
Conclusions
Our data showed overexpression of IL-6 and STAT3 in OPA in comparison with healthylungs. These results suggest a potential role of IL6-STAT3 in OPA carcinogenesis.
... In the present study, observations of macroscopic and microscopic pathology were in line with the specifications mentioned in other studies. 11,12,[31][32][33][34] Any kind of damages and acquired mutations of the TP53 gene disabled the gene and causes the escape of cancer cells to escape from apoptosis and eventually becomes carcinogenesis. Prevalence of TP53 mutations in more than ten thousand tumor indicates that the tumor origin depends entirely on the possibility of TP53 mutation, for example, the TP53 mutation frequency in lung neoplasia is more than 46.00%, about 34.00% of breast tumors, and in leukemia, is less than 6.00%. ...
Ovine pulmonary adenocarcinoma (OPA) is a model of human lung cancer and fatal viral disease that causes neoplasia in sheep respiratory cells. In the current study, 986 lung samples was inspected in the slaughterhouse, and finally twenty OPA lung organs were clinically diagnosed and five healthy lung organs were assigned as the control sample. Three SSCP patterns were detected for the affected lungs animals in comparison with the healthy lungs. In addition, sequencing results indicated three different single point mutations in exon 4 of TP53 within infected lungs, whereas no mutations were observed in exon 9 of this gene. Real-time PCR results showed up-regulation of the TP53 gene in all the infected lung cells compared to healthy cells. There was significant correlation between the mutations in exon 4 and OPAand can be used as a useful tool in determining the mechanism of lung cancer.
... Infection such Lentivirus, which leads to the development of Maedi-Visna disease in sheep, which develops interstitial pneumonia (Pinczowski et al. 2017). Another infectious disease to be ruled out is pulmonary adenomatosis, which is caused by the Jaagsiekte sheep retrovirus (JSRV), characterized by forming papillary or acinar adenocarcinoma (García-Goti et al. 2000). In these cases, the exclusion was performed by epidemiology and histological findings. ...
Poisoning by Trema micrantha commonly causes hepatocellular necrosis in cattle, sheep, and goats and edema and cerebral hemorrhage in horses. This plant can cause toxic pneumopathy in sheep, and there is only one report of the natural form and one of the experimental form in the State of Rio Grande do Sul. This study aimed to report an outbreak of the respiratory form of natural poisoning by T. micrantha in sheep. Six sheep developed clinical respiratory signs after consumption of the plant and four of them died and two recovered after treatment with dexamethasone. The sheep presented tachypnea, noisy breathing, edema of the face, eyelids, and vulva, and subcutaneous emphysema on the face and neck. Necropsy (Sheep 2, 3, and 4) showed uncollapsed, heavy, diffuse red lungs with evident costal impressions and a moderate amount of serosanguineous fluid flowed at section. The liver had a moderate diffuse evident lobular pattern. The histopathology of the lungs of the three necropsied sheep showed congestion and edema with the formation of hyaline membranes within accentuated diffuse alveoli, in addition to thickening of the alveolar septa due to mild to moderate diffuse type II pneumocyte hyperplasia and also mild to moderate diffuse infiltrate of macrophages, lymphocytes, plasma cells, and neutrophils in the lumen of alveoli, bronchi, and bronchioles. Sheep 3 also showed type II pneumocytes with enlarged and hyperchromatic nuclei, sometimes binucleated with evident nucleoli, and, in some regions, the pneumocytes were desquamated to the alveolar lumen forming small syncytia and mild multifocal hyperplasia in the bronchial epithelium. The anti-cytokeratin IHC evaluation showed marked diffuse intracytoplasmic staining in hyperplastic type II pneumocytes in the bronchiolar epithelium of the three evaluated sheep. The liver of the three sheep had mild multifocal centrilobular necrosis. It seems to be the second report of spontaneous poisoning by T. micrantha in sheep developing lung lesions described in Brazil and the first in the State of Santa Catarina.
... Ainsi, in vitro, des lignées cellulaires ovines de diverses origines tissulaires peuvent être infectées par le JSRV alors que la production virale reste faible [32]. La présence d'ADN proviral peut être mise en évidence dans les ganglions lymphatiques, divers tissus lymphoïdes, les macrophages alvéolaires et les cellules mononucléées du sang périphérique dont les monocytes et les lymphocytes B et T [30,[33][34][35][36]. La protéine de capside est exprimée dans les cellules lymphoïdes des noeuds lymphatiques médiastinaux drainant les tumeurs [34] et le rein. ...
JSRV (jaagsiekte sheep retrovirus) is a betaretrovirus, infecting small ruminants. This virus is responsible for the development of pulmonary adenocarcinoma, by the transformation of epithelial cells of the bronchioli and alveoli. This animal cancer is related to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral etiology has been proposed for several decades. In small ruminants JSRV interacts with the cells through the Hyal2 receptor. JSRV genome is simple and does not contain already known oncogene. It is now well established that the envelope protein is oncogenic by itself, via the cytoplasmic domain of the transmembrane glycoprotein and some domains of the surface glycoprotein. Activation of the PI3K/Akt and MAPK pathways participates to the envelope-induced transformation. The tumour development is associated with telomerase activation.
... OPA is an infectious tumor of sheep lungs that in its so-called classical form can be very similar to a complicated case of pulmonary SRLV infection, sometimes only distinguishable by histopathology (García- Goti et al., 2000). Grossly, in a case of OPA, palpation of the cranial lobes of the lung would notice a remarkable hard, fibrotic touch, there would be satellite tumors of at least 0.5-1 cm close to the main tumor mass and the color of the remaining lung would be generally normal (Fig. 3). ...
Pulmonary affection is by far the most severe and widespread disease form caused by Small Ruminant Lentiviruses (SRLV)in sheep. The infection implies direct contact between animals and the most important infection route is by the respiratory tract. Disease is insidious and might be seen in one-year-old animals onwards. Non-productive dyspnea is the most common clinical sign and interstitial pneumonia with increased lung size and volume are the pathologic landmarks. Early detection of infected animals is a key step for the diagnosis and it is best achieved by third generation ELISAs that include a multistrain design to detect divergent genotypes. Differential diagnosis must be established with ovine pulmonary adenocarcinoma, the visceral form of ovine caseous lymphadenitis, ovine respiratory complex, gangrenous pneumonia and bacterial and parasitic (Dyctiocaulus filaria, Oestrus ovis)infections. Control is achieved by combining serological and management measures and is based on total or selective culling of infected animals and replacement with uninfected lambs. Serological segregation and replacement with the offspring of seronegative ewes is also a suitable option for control. Selection of resistant sheep might be a future option. Pulmonary affection by SRLV in sheep must be taken into account in the face of a chronic, non-productive dyspnea.
... Ainsi, in vitro, des lignées cellulaires ovines de diverses origines tissulaires peuvent être infectées par le JSRV alors que la production virale reste faible [32]. La présence d'ADN proviral peut être mise en évidence dans les ganglions lymphatiques, divers tissus lymphoïdes, les macrophages alvéolaires et les cellules mononucléées du sang périphérique dont les monocytes et les lymphocytes B et T [30,[33][34][35][36]. La protéine de capside est exprimée dans les cellules lymphoïdes des noeuds lymphatiques médiastinaux drainant les tumeurs [34] et le rein. ...
JSRV (jaagsiekte sheep retrovirus) is a betaretrovirus, infecting small ruminants. This virus is responsible for the development of pulmonary adenocarcinoma, by the transformation of epithelial cells of the bronchioli and alveoli. This animal cancer is related to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral etiology has been proposed for several decades. In small ruminants JSRV interacts with the cells through the Hya12 receptor. JSRV genome is simple and does not contain already known oncogene. It is now well established that the envelope protein is oncogenic by itself, via the cytoplasmic domain of the transmembrane glycoprotein and some domains of the surface glycoprotein. Activation of the PI3K/Akt and MAPK pathways participates to the envelope-induced transformation. The tumour development is associated with telomerase activation.
... OPA tumors originate from type II pneumocytes and Clara cells. Metastases in intra-thoracic tissues have been reported in many studies (Garcia-Goti et al. 2000, Minguijon et al. 2013, but research related to extrathoracic metastases has been limited. The most typical feature of clinical OPA is the discharge of a whitish foamy fluid from the nostrils. ...
The aim of this study is to detect the exogenous Jaagsiekte sheep retrovirus (exJSRV) in suspected cases of ovine pulmonary adenocarcinoma (OPA) from the Eastern Anatolian region of Turkey. Pathological examination and PCR were carried out with the lung, lymph nodule, brain, heart and liver tissues of four sheep with suspected OPA. Histology of the lung sections indicated the well-circumscribed, multifocal and unencapsulated gray to white masses (arrows) on the parietal surface of medial and caudal lobes. exJSRV was detected in all tissue samples except for brain by nested polymerase chain reaction (nPCR). In addition to the nested-PCR results, the presence of exJSRV into the clinical samples was confirmed with sequencing of two PCR-positive products for OPAV. This report highlights the first presence of exJSRV in the sheep suspected with OPA in Turkey. Furthermore, the results provide supporting evidence for the metastasis of exJSRV in extra-thoracic tissues. © 2015 Agricultural Research Communication Centre. All rights reserved.
... In naturally infected animals, viral DNA can be detected in lymphoid tissues, blood mononuclear cells, e.g., monocytes or B or T lymphocytes and alveolar macrophages (Palmarini et al., 1996;Holland et al., 1999;Garcia-Goti et al., 2000;Gonzalez et al., 2001;Salvatori et al., 2004). The virus burden is higher in adherent mononuclear cells than in non-adherent lymphocytes (Holland et al., 1999). ...
... The gross and histomorphological features described in this study are similar to those observed earlier 12,31 . Accumulation of macrophages within apparently normal alveoli beside affected alveoli was a consistent feature in adenomatosis which is in agreement with other reports 32,33,34,35,36,37 . Atelectasis was seen associated with most of the cases of pneumonia but 3 cases (1.48%) manifested changes of atelectasis in pure form with no associated pathology. ...
Respiratory disorders are very common in sheep and often not easily detectable in the live animals until it is complicated. Thus examination of lungs at slaughter is the only way to understand pathology behind respiratory disorders and their prompt diagnosis. And thus this study was aimed at documenting various pathological conditions affecting the lungs of sheep. A total number of 903 sheep carcasses were examined, out of which, lung lesions were recorded in 203 cases (22.48%). Pneumonia was recorded in 16.82% (152/903) cases, adenomatosis in 4.87% (44/903) cases and other lesions (atelectasis, emphysema and hemorrhages) in 0.78% (7/903) of cases. Based on duration of inflammation, involvement of tissue component and the principal constituent of the exudates, the lung lesions were further classified as acute bronchopneumonia (90/203 cases, 44.33%), sub-acute bronchopneumonia (28/203 cases, 13.79%), chronic bronchopneumonia (7/203 cases, 3.45%), acute interstitial pneumonia (16/203 cases, 7.88%), chronic interstitial pneumonia (6/203 cases, 2.96%), broncho-interstitial pneumonia (4/203 cases, 1.97%), embolic pneumonia (1/203 cases, 0.49%), adenomatosis (44/203 cases, 21.68%), atelectasis (3/203 cases, 1.48%), emphysema (1/203 cases, 0.49%) and hemorrhages (3/203 cases, 1.48%).
... In the present study, accumulation of macrophages within the apparently normal alveoli beside affected alveoli was a prominent feature in the tumor. This is in agreement with other reports 14,15,16,17,18,19 . Ovine pulmonary adenocarcinoma derived, transformed alveolar type II cell lines have been demonstrated to produce a macrophage chemotactic factor which might serve as a mechanism for recruiting macrophages into OPA affected lungs. ...
Ovine pulmonary adenocarcinoma (OPA) or ovine pulmonary carcinomatosis (previously known as ovine pulmonary adenomatosis) is a contagious tumour forming viral disease caused by the genus beta-retrovirus of retroviridae (jaagsiekte sheep retrovirus). This study was aimed to understand the prevalence of disease in the locality based on histopathological diagnosis and its correlation with age, sex and breed. Out of 903 sheep carcasses examined, OPA was recorded in 44 cases accounting to 4.87%. The gross lesions varied from multifocal greyish nodules to complete consolidation of the lung parenchyma. Histologically, there were single to multiple layers of cuboidal to columnar epithelial cells giving adenomatous appearance. The cuboidal or columnar tumour cells replaced the normal alveolar epithelia and in some cases it formed into papilliform growths that projected into the alveoli. The peribronchial and peribronchiolar lymphoid aggregates were consistent features in most of the cases studied. Argyrophilic nucleolar organizer regions (AgNORs) were counted in representative cases of nodular and consolidated forms of adenocarcinomatosis to assess the rate of cell proliferation. The average AgNOR counts per nucleus were 4.672 ± 0.68 and 3.086 ± 0.537 for nodular and consolidated forms respectively.
... The gross and histomorphological features described in this study are similar to those observed earlier 12,31 . Accumulation of macrophages within apparently normal alveoli beside affected alveoli was a consistent feature in adenomatosis which is in agreement with other reports 32,33,34,35,36,37 . Atelectasis was seen associated with most of the cases of pneumonia but 3 cases (1.48%) manifested changes of atelectasis in pure form with no associated pathology. ...
Respiratory disorders are very common in sheep and often not easily detectable in the live animals until it is complicated. Thus
examination of lungs at slaughter is the only way to understand pathology behind respiratory disorders and their prompt diagnosis. And thus
this study was aimed at documenting various pathological conditions affecting the lungs of sheep. A total number of 903 sheep carcasses
were examined, out of which, lung lesions were recorded in 203 cases (22.48 %). Pneumonia was recorded in 16.82% (152/903) cases,
adenomatosis in 4.87% (44/903) cases and other lesions (atelectasis, emphysema and hemorrhages) in 0.78% (7/903) of cases. Based on
duration of inflammation, involvement of tissue component and the principal constituent of the exudates, the lung lesions were further
classified as acute bronchopneumonia (90/203 cases, 44.33%), sub-acute bronchopneumonia (28/203 cases, 13.79%), chronic
bronchopneumonia (7/203 cases, 3.45%), acute interstitial pneumonia (16/203 cases, 7.88%), chronic interstitial pneumonia (6/203 cases,
2.96%), broncho-interstitial pneumonia (4/203 cases, 1.97%), embolic pneumonia (1/203 cases, 0.49%), adenomatosis (44/203 cases,
21.68%), atelectasis (3/203 cases, 1.48%), emphysema (1/203 cases, 0.49%) and hemorrhages (3/203 cases, 1.48%).
Ovine pulmonary adenocarcinoma (OPA) is an important viral-induced neoplasia in sheep caused by exogenous Jaagsiekte sheep retrovirus (exJSRV). Coinfection of exJSRV and Maedi-Visna virus (MVV) is reported in OPA cases, but its worldwide distribution and significance on lung pathology is not yet completely understood. This study aimed to investigate the MVV coinfection rate in 82 exJSRV-related OPA cases, and their pathological effects on lung parenchyma in slaughtered sheep in Transylvania (Romania). On gross examination, classical form of OPA was identified in 92.7%; no changes consisting with MVV interstitial pneumonia were identified in the included cases. The most common histological type of OPA was acinar (58.5%) and the myxoid growths were found in 18 cases. The exJSRV and MMV coinfection rate in examined sheep was 47.6% (39/82). The assessment of perineoplastic areas from coinfected animals, revealed interstitial lymphoplasmacytic infiltrates in all cases, lymphoid hyperplasia in 60.6% cases (20/33) and fibromuscular hyperplasia in 63.7% (21/33). This is the first report providing new data on distribution of OPA coexisting with MVV infection in slaughtered sheep in Romania. We consider that the OPA and MVV coinfection may play an important role on the severity of ovine chronic pulmonary diseases and further studies are needed to confirm this hypothesis.
Les cancers sont un groupe de maladies diverses et complexes responsables de millions de décès chaque année à travers le monde. Ces maladies sont multicausales et peuvent être engendrées par de nombreux facteurs génétiques ou environnementaux. Parmi les facteurs susceptibles de déclencher l’oncogénèse, les agents infectieux (virus, bactéries et parasites) sont à l’origine de plus de 16 % des cancers. Parmi les virus, l’étude de la famille des Retroviridae a permis de comprendre les mécanismes de l’oncogénèse virale. Certains rétrovirus portent des oncogènes d’origine cellulaire, d’autres activent des oncogènes cellulaires lors de leur insertion dans le génome de l’hôte et d’autres enfin portent des protéines virales oncogènes. Parmi ces derniers, le ré trovirus JSRV (Jaagsiekte Sheep Retrovirus) est responsable de l’adénocarcinome pulmonaire ovin chez les petits ruminants. JSRV transforme des cellules épithéliales alvéolaires et bronchiolaires via sa protéine d’enveloppe (Env) qui dérégule des voies de signalisation cellulaire contrôlant la prolifération, dont la voie Akt/mTOR (Phosphatidylinositol 3-kinase Alpha serine-Threonine-protein Kinase/ mammalian Target Of Rapamycin). Nous avons identifié la protéine cellulaire RALBP1 (RalA Binding Protein 1) comme un partenaire de Env et analysé les effets de cette interaction sur la transformation induite par JSRV. Nous avons confirmé la formation de complexes protéiques RALBP1/ Env dans les cellu les de mammifères. Par inhibition de l'expression de RALBP1 avec des siRNA spécifiques, nous avons montré que la protéine cellulaire est impliquée dans le processus de transformation cellulaire induite par l’ enveloppe et dans la modulation de la voie mTOR /p70S6K. Nous avons mis en évidence la sous-express ion de RALBP1 dans les cellules exprimant Env in vitro , mais aussi ex vivo dans les cellules primaires tumorales et in vivo dans les tissus tumoraux. Nous avons déterminé que CDC42, un activateur de p70S6 K dont l’activité est négativement régulée par RALBP1, interagit avec l’enveloppe de JSRV. Nous avons posé l’hypothèse que la diminution de RALBP1 provoquée par l’Env activerait CDC42 ce qui conduirait à l’activation p70S6K. CDC42 étant impliqué dans l’organisation du cytosquelette d’actine, nous nous sommes intéressés à l’effet de l’enveloppe sur le cytosquelette d’actine. Nous avons mis en évidence une désorganisation du cytosquelette d’actine et une perte de la polarisation des cellules exprimant l’enveloppe de JSRV. Comme de nombreux autres virus, JSRV pourrait moduler le cytosquelette d’actine des cellules épithéliales qu’il infecte afin de désorganiser l’épithélium et ainsi affecter son hôte plus efficacement. Mots clés : rétrovirus, JSRV, RALBP1, transformat ion cellul
Ovine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus (exJSRV). The prevalence of JSRV-related OPA in Eastern European countries, including Romania is unknown. We aimed to investigate: the prevalence and morphological features of OPA (classical and atypical forms) in Romania, the immunophenotype of the pulmonary tumors and their relationships with exJSRV infection. Lung tumors from 28 slaughtered adult sheep and 6 necropsied individuals were grossly evaluated. Cytology, histology, immunocytochemistry, immunohistochemistry, electron microscopy and DNA testing were subsequently performed. Out of 2693 examined sheep, 34 had OPA (1.26% prevalence). The diaphragmatic lobe was the most affected. Grossly, the classical OPA was identified in 88.24% of investigated cases and the atypical OPA in 11.76% that included solitary myxomatous nodules. Histopathology results confirmed the presence of OPA in all suspected cases, which were classified into acinar and papillary types. Myxoid growths (MGs) were diagnosed in 6 classical OPA cases and in 2 cases of atypical form. JSRV-MA was identified by IHC (94.11%) in both epithelial and mesenchymal cells of OPA. Immunocytochemistry and electron microscopy also confirmed the JSRV within the neoplastic cells. Adenocarcinoma was positive for MCK and TTF-1, and MGs showed immunoreaction for Vimentin, Desmin and SMA; Ki67 expression of classical OPA was higher than atypical OPA and MGs. Phylogenetic analysis revealed the presence of the exJSRV type 2 in Romanian sheep affected by lung cancer and showed a high similarity with the UK strain (AF105220.1), confirming exJSRV2 for the first time in Romania. Additionally, we described the first report of atypical OPA in Romania, and to the best of our knowledge, in Eastern Europe. Finally, we showed that MGs have a myofibroblastic origin.
Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). JSRV infection is usually detected post-mortem by macroscopic and histological examination of lungs for lesions of OPA. Subsequently, the presence of JSRV may be confirmed using polymerase chain reaction (PCR) on tumour tissue. Our goal was to determine the most effective way of combining macroscopic and histological examination with reverse transcriptase PCR (RT-PCR) to detect JSRV infection post-mortem. Lungs of slaughtered sheep (n = 369) with macroscopic lesions were examined macroscopically and histologically to identify lesions consistent with OPA, and subsequently subjected to RT-PCR for JSRV. Positive (Ppos) and negative (Pneg) agreement and Cohen’s Kappa were calculated between RT-PCR and: 1) macroscopic examination; 2) histological examination; 3) macroscopic and histological examinations combined in series, and 4) in parallel. The highest Ppos was between macroscopic and histological examination in parallel and RT-PCR (0.38). Conversely, Pneg for all combinations of RT-PCR and macroscopic and histological examinations was high (0.95-0.96). All Kappa values were low (0.1-0.33). This indicates that macroscopic and histological examination combined in parallel is the most effective way to identify animals that should be tested using RT-PCR for JSRV. If a positive result is obtained on macroscopic examination and/or histological examination, RT-PCR for JSRV should be carried out. The high Pneg indicates that if a negative result is obtained on macroscopic and histological examination, RT-PCR testing is not merited, as the result is likely to be negative. This provides an evidence-base for the diagnosis of JSRV infection.
Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV), which induces the transformation of secretory epithelial cells of the distal respiratory tract. The disease has been recorded in the major sheep rearing areas with the exceptions of Australia and New Zealand, and is clinically characterized by a chronic respiratory process that often involves the production of pulmonary fluid that is discharged from the nostrils in final stages of the disease while the “wheelbarrow” test is performed. The respiratory route has been accepted to be the most important natural mode of transmission for JSRV but colostrum and milk can transmit JSRV to lambs. In OPA affected flocks, under endemic conditions, JSRV infected sheep may be present in a high proportion but very few of them develop clinical signs. Such apparently healthy animals are responsible for the spread of the disease because is difficult to identify infected animals or preclinical stages. There are not serological diagnostic tests due to the lack of a detectable immune response in JSRV infected animals, and although blood molecular tests are available their sensitivity is low. For this reason the disease has failed to be controlled so far and continues to cause significant economic losses. Control strategies based on colostrum and milk management have been demonstrated to be effective but expensive for most commercial flocks. In the recent years efforts for controlling the disease have focussed on searching methods for early diagnosis and the next future seems to be the establishment of low risk status for OPA in the flocks. Nevertheless, working on improving the identification of infected animals is essential for the implementation of effective strategies for OPA eradication.
Ovine pulmonary adenocarcinoma (OPA) is a retroviral disease of sheep and occurs usually in two forms viz. classical and atypical, which differ in their histological lesions, cellular infiltrates, behaviour and prognosis. Present investigation was focussed to evaluate the differential expression of various tumour biomarkers in both OPA forms. Among 23 lung tissue samples suspected for OPA, histopathological examination diagnosed 12 as classical OPA, 6 as atypical OPA and 5 as bronchiolar hyperplasia. Polymerase chain reaction with LTR (long terminal repeat)-specific primers revealed that all classical and atypical OPA cases and three bronchiolar hyperplasia cases were positive for Jaagsiekte sheep retrovirus (JSRV) genome. Immunohistochemical (IHC) staining showed that JSRV capsid antigen was localized in the proliferating alveolar pneumocytes, bronchiolar epithelium and MNCs (mononuclear cells). Expression of PCNA was comparatively higher in classical OPA than atypical OPA and bronchiolar hyperplasia. Atypical OPA had higher MHC II expression than classical form indicated the higher proliferation of fibroblasts. FOXO3a expression is comparatively higher in OPA cases with mild inflammatory reaction while MMP2 expression was higher in OPA cases with severe inflammatory reaction. In conclusion, classical OPA is more proliferative and expansive in nature as compared to the atypical form. Further controlled study is required to prove the prognostic and metastatic potential of these markers in OPA.
Ovine pulmonary adenocarcinoma (OPA) was studied in the lungs of 15 naturally-affected sheep (9 with classical and 6 atypical lesions) by transmission electron microscopy. Two lung samples from normal sheep were used to develop the ultrastructural criteria. Pathologic lesions consisted of focal-multifocal to coalescent nodules or masses in the cranioventral or diaphragmatic lobes. Ultrastructural characteristics of tumor cells in the alveoli and bronchioles allowed categorization of these cells into three groups; neoplastic alveolar type (AT) Φ cells in the alveoli contained numerous cytoplasmic lamellar bodies, well developed rough endoplasmic reticulum and glycogen particles; neoplastic clara cells in the bronchioles contained apical electron-dense granules and well-developed smooth endoplasmic reticulum; undifferentiated tumor cells in the alveoli and bronchioles lacked characteristic lamellar bodies or electron-dense granules. Neither complete virions nor viral inclusions were seen in the neoplastic cells. In the present study, there were no ultrastructural differences in the neoplastic cells between classical and atypical forms. It seems that type II pneumocytes and clara cells are the origin of the neoplasia in the alveoli and bronchioles, respectively.
Sheep (ovine) pulmonary adenocarcinoma (SPA), also known as ovine pulmonary adneomatosis (OPA), jaagsiekte and ovine pulmonary carcinoma (OPC) is a contagious lung tumor in sheep and, more rarely, in goats. This study was carried out in Khuzestan, in the southwest of Iran for a period of six months. A total number of 3985 native breed goats were clinically inspected and postmortem examination was recorded at the abattoir in Ahvaz. In necropsy 4 of these goats showed gross pulmonary lesions characteristic of classical pulmonary adenomatosis. The lungs were usually heavy and appeared "waterlogged", but affected areas of the lungs were solid and light grey in color, and tissue looked slightly translucent. The cut surface showed numerous small, slightly-elevated white-grey nodules in each section. The affected alveoli in these areas were lined by proliferating cuboidal cells forming irregular folds and papillary projections. The bronchi and the bronchioles exhibited moderate epithelial hyperplasia and metaplasia. The bronchial associated lymphoid tissue and the smooth muscles of terminal and respiratory bronchioles were hyperplastic. The affected areas were essentially the same and also nearly similar to previous reports.
Jaagsiekte sheep retrovirus (JSRV) is an exogenous betarerovirus that causes a contagious form of lung cancer in sheep termed ovine pulmonary adenocarcinoma (OPA). OPA is derived from oncogenically transformed secretory lung epithelial cells, type II pneumocytes, and Clara cells located in the distal airways. In vitro and in vivo studies demonstrate that the envelope protein (Env) is an oncogene because its expression alone can transform cells in culture and induce tumors in animals. Model systems to study Env transformation and mechanisms of transformation are discussed. Although JSRV can infect numerous cell types, pathology is largely restricted to the lung because the viral LTR is only transcriptionally active in differentiated airway epithelial cells. The transcriptional specificity of the JSRV LTR and its role in disease outcome are discussed. Sheep contain endogenous copies of JSRV, some of which are important in embryonic development (placentation), and others serve as restriction factors for exogenous JSRV infections.
The possibility of jaagsiekte sheep retrovirus (JSRV) genome detection in peripheral blood leukocytes and respiratory tract fluid of ovine pulmonary adenocarcinoma (OPA) affected sheep was tested. Five of six lambs used in the experiment were infected with JSRV by intratracheal inoculation. The blood samples were taken from all the lambs at 10-d intervals for 3 months and the white blood cells were subjected to DNA isolation followed by PCR amplification for the detection of proviral DNA that gave negative results for all the samples. The respiratory tract fluid was collected from the nostrils of lamb No. 6, which developed clinical sign of OPA 2 months after the inoculation. The fluid was examined using PCR and reverse transcriptase PCR (RT-PCR) for the presence of proviral DNA or viral RNA. The presence of OPA in the lamb was subsequently confirmed by histopathological examination and the detection of proviral DNA in the lung tissue. Results of the standard PCR amplification performed on the DNA isolated from the nasal discharge from lamb No. 6 was negative, while the RT-PCR gave positive results confirming the presence of virions in the lung fluid. Results of the study show the RT-PCR technique may be a useful tool in ante-mortem diagnosis of OPA, especially in distinguishing it from other respiratory diseases.
In the years from 1989 to 2000 thirteen sheep affected with sheep pulmonary adenomatosis were detected in Styria. The cases are described by their clinical signs and their pathologic changes. Particularly striking were the results of the lung examinations of diseased sheep, the high lung weight and the rubbery texture of infected lung areas. Epizootiology was investigated by means of anamnestic inquiries in the affected herds. They showed, that all seven cases in Blackface-sheep are obviously related to one certain flock. Also the three cases in Merinoland-sheep depend on each other. The last case in a dairy sheep farm also occurred in a purchased animal.
Ovine pulmonary adenomatosis (OPA) is a contagious bronchio-alveolar carcinoma that is caused by Jaagsiekte sheep retrovirus. The virus induces transformation in Clara cells and pneumocyte type II. In the present study, 42 grossly suspected lungs of slaughtered sheep to OPA were collected. Lungs were enlarged, failed to collapse with distribution of firm greyishwhite nodules on the cranioventral or diaphragmatic lobes and some of them contained foamy fluid in their airways. The lung samples were taken for histopathologic, PCR and immunohistochemistry investigations. Histopathologically, 16 lungs (n=16/42) showed neoplastic foci that were composed of proliferated pneumocytes type II and Clara cells arranged in the acinar or papillary growth pattern. Immunohistochemical analysis detected JSRV capsid protein (JSRV-CA) in the cytoplasm of pneumocytes type II and Clara cells. PCR technique was done on 16 paraffin embedded and fresh frozen tissues. Based on PCR technique targeting U3 region, amplicons of expected size (176 bp) were observed in all 15 paraffin embedded and 16 fresh frozen sections. No positive results were detected in the apparently normal lungs. It seems PCR can be used on paraffin-embedded tissues to reveal Jaagsiekte sheep retrovirus infection, but complementary studies on a large number of samples are required to determine sensitivity.
It was an honor to be asked by Drs. Jubb, Kennedy, and Palmer to assume the editorship of Pathology of Domestic Animals. I studied from the first edition in Saskatoon as a DVM student, used the second edition as a working pathologist, and encouraged production of, and contributed to, the third and fourth editions. I'm delighted to have been able to be part of this continuum. In this age of instantaneous global communication and virtually universal access to databases through powerful search engines, does the need continue for such print versions of textbooks? I firmly believe that printed books continue to serve a useful function, partly through their portability and ease of use, but primarily through provision of a measured overview of important topics, with the relevance of competing topics put into perspective by authorities in the field. In particular, this latest edition of these volumes is offered as a comprehensive, and we hope beneficial, overview of the diseases of the major domestic mammals.
The 5th edition of Jubb, Kennedy, and Palmer's Pathology of Domestic Animals continues the long tradition of this classic set of volumes as the most comprehensive reference book published on the topic of pathology of the common domestic mammals, with emphasis on disease conditions of cattle and small ruminants, swine, horses, dogs and cats. Using a body systems approach, recognized authorities in their fields provide overviews of general characteristics of the system, reactions to insult, and disease conditions broken down by type of infectious or toxic insult affecting the anatomical subdivisions of each body system. Since the publication of the 4th edition in 1993, much has changed. Disease agents, such as Bovine viral diarrhea virus (BVDV) type 2, Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine circovirus 2, Hendra virus, and Leptospira spp., have emerged or further evolved. Molecular-based testing, including polymerase chain reaction (PCR) and in-situ hybridization, have allowed further understanding of pathogenesis of disease, and have greatly furthered our diagnostic capabilities. Thoroughly revised text, including new or evolving pathogens and new diagnostic techniques. Over 250 new illustrations. Maintains the currency of the text, assists the reader in putting new conditions into perspective. Updating of the Bibliography on each subject gives readers new entry points into the rapidly expanding literature on each subject. Illustrations of new conditions or agents. Reader-friendliness improved through highlighting of text, bullet-point lists, italics, diagnostic hints.
Resumen. Se describen los aspectos clínicos, anatomopatológicos, histopatológicos e inmunohistoquímicos de Adenomatosis pulmonar ovina en un animal nativo de la puna de Jujuy, noroeste de Argentina. Se observaron síntomas respiratorios severos. y eliminación de secreciones seromucosas profusas por las fosas nasales. A la necropsia se observaron pulmones sin colapsar, con nodulaciones firmes coalescentes de color grisáceo marmóreo, sobre la mitad ventral de lóbulos pulmonares. La tráquea y el árbol bronquial se encontraban obliterados con abundante espuma blanquecina. Histopatologicamente se observó proliferación del epitelio alveolar de células columnares (neumocitos tipo II), con proyecciones papilares intraalveolares y sectores con formaciones de aspecto acinar con abundante proliferación de macrófagos alveolares en áreas circundantes a sectores tumorales. Se observó además proliferación de células de Clara bronquiolares con proyecciones papilares intraluminales. El virus Jaagsiekte fue demostrado por técnicas de inmunohistoquímica. Estudios posteriores en la región son necesarios para la caracterización epidemiológica. Summary. The clinical, pathological, histopathological and immunohistochemical aspects sheep pulmonary adenomatosis are descripted in an animal native to the highlands of Jujuy, northwestern Argentina. Severe respiratory symptoms were observed. Seromucous secretions and profuse elimination of the nostrils are observed. At necropsy, lungs were observed without collapsing, firm nodules coalescing with gray marble aspect, about half ventral lung lobes. The trachea and bronchial tree were obliterated with plenty of white foam. Histopathologically, proliferation alveolar epithelium of columnar cells (type II pneumocytes), alveolar and papillary projections sectors looking acinar formations with abundant proliferation of alveolar macrophages in areas
The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. The genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type B and D oncoviruses. Comparison of the amino acid sequences of JSRV proteins with those of other retrovirus proteins and phylogenetic studies suggest that JSRV diverged from its type B and D lineage after the type B mouse mammary tumor virus but before the type D oncoviruses captured the env gene of a reticuloendotheliosislike virus. Southern blot studies show that closely related sequences are present in sheep and goat normal genomic DNA, indicating that JSRV could be endogenous in ovine and caprine species.
Five sheep with ovine pulmonary carcinoma were markedly dyspneic and had sporadic coughing; two had copious watery nasal exudate. In four, lesions consisted of multifocal nodules of neoplastic cuboidal epithelial cells in acinar or papillary patterns. Electron microscopically, cells had microvilli, tight junctions, and cytoplasmic lamellar bodies typical of alveolar type II cells. One sheep had a single lung tumor of nonciliated bronchiolar epithelial cells. Vacuolated alveolar macrophages surrounded adenomatous foci. One sheep had a metastatic lesion in the caudal mediastinal lymph node. All sheep had histologic lesions of lymphoid interstitial pneumonia (LIP, ovine progressive pneumonia) consisting of peribronchiolar and interstitial lymphoid hyperplasia, and fibromuscular proliferation; all had serum precipitating antibodies to ovine lentivirus. Lung fluids or tumor homogenates contained a 26-kd peptide that crossreacted with a primate-derived type D retrovirus as detected by immunoblotting or interspecies competition radioimmunoassay. Ovine lentivirus was isolated from concentrated lung fluids or tumor tissues of four sheep tested and from tumor cell DNA of one animal transfected into ovine muscle cells. These studies document the presence of type D-related retrovirus antigen in ovine pulmonary carcinoma (OPC) in the United States and indicate that lentivirus-induced LIP is a lesion frequently associated with this disease.
Two retrovirus-associated pulmonary diseases of sheep [ovine pulmonary carcinoma (OPC); sheep pulmonary adenomatosis], a bronchoalveolar carcinoma, and lymphoid interstitial pneumonia (LIP) were induced simultaneously in 9 of 9 neonatal lambs. The lambs were killed 8-28 weeks after intratracheal injection of lung tumor homogenate or lung fluid derived from sheep with naturally occurring OPC and ovine lentivirus (OvLV) infection. The inoculated lambs developed multifocal neoplasms of alveolar type II cells or nonciliated bronchiolar epithelial cells, LIP, and pulmonary lymph node hyperplasia, and all produced antibody to OvLV. OvLV was isolated from 6 to 7 lambs tested, and infectious center assay of pulmonary lavage cells from 3 lambs revealed that approximately 1 in 1,000 pulmonary lavage cells contained infectious lentivirus. Neither contact control lambs nor control lambs that received ultrafiltered lung fluid developed evidence of either disease or of OvLV infection. Lung fluid or tumor tissue of lambs with OPC contained a 26,000-dalton protein that cross-reacted with antiserum to p27 to Mason-Pfizer monkey virus, a type D retrovirus. The fact that no antigenic cross-reaction between OvLV and type D retroviruses has been demonstrated supports the presence of two retroviruses in sheep with OPC. Although the contributions of each agent to oncogenesis in this model are difficult to evaluate, the rapid development of two retrovirus-induced pulmonary diseases in experimentally inoculated lambs suggests an etiologic or pathogenetic synergism between these two members of the family Retroviridae.
Sheep pulmonary adenomatosis (SPA) is a naturally occurring contagious lung tumour of sheep which has been associated aetiologically with a type D- and B-related retrovirus (Jaagsiekte retrovirus; JSRV). To improve understanding of the aetio-pathogenesis of SPA, the distribution and the sites of JSRV replication in sheep with naturally or experimentally induced SPA or in unaffected controls were identified. New immunological reagents were produced and a blocking enzyme-linked immunosorbent assay (B-ELISA) and an immunohistochemical technique for the detection of JSRV major capsid protein at the tissue and cellular levels were developed. JSRV was detected only in the respiratory tract of sheep affected by pulmonary adenomatosis and specifically in the transformed epithelial cells of the alveoli of SPA-affected sheep.
Ovine pulmonary carcinoma (OPC) is a contagious lung cancer of sheep that is presumed to be caused by an exogenous retrovirus of sheep, jaagsiekte sheep retrovirus (JSRV). The sheep genome carries 15 to 20 copies of endogenous sheep retrovirus (ESRV) loci that hybridize to JSRV DNA probes. In order to clarity the etiologic roles of ESRV and an exogenous JSRV-like retrovirus (exJSRV) in OPC, we assessed sequence differences between ESRV and JSRV. Molecular characterization of six ESRV loci revealed restriction sites specific for JSRV. Nucleotide sequences of ESRVs from sheep of different breeds were similar to those of JSRV in structural genes but divergent in U3. Therefore, primers specific for the U3 sequences of exJSRV were designed for use in the PCR. Of 13 tumor DNAs tested by PCR with these exogenous-virus U3 primers, 8 produced DNA fragments that hybridized with the JSRV gag probe, but neither lung DNAs from healthy sheep nor DNAs from nontumor tissues of diseased sheep produced similar DNA fragments. exJSRV PCR products from tumor DNAs of sheep with OPC from three continents had restriction profiles similar to each other but different from those of ESRVs upon digestion with EcoRI, HindIII, NdeI, KpnI, and ScaI. These exjSRVs could be classified into two genotypes according to U3 sequences and restriction profiles. U3 sequences of exJSRV proviruses in tumors strongly resembled those of JSRV but differed from those of ESRVs, suggesting that exJSRVs, rather than ESRVs, are primarily associated with oncogenesis in OPC.
Jaagsiekte retrovirus (JSRV) is an exogenous type D-related retrovirus specifically associated with a contagious lung cancer of sheep (sheep pulmonary adenomatosis; SPA). Recently, epithelial tumour cells in the lungs of SPA-affected sheep were identified as major sites of JSRV replication by immunological techniques and RT-PCR amplification of part of JSRV gag. JSRV was not detected outside the lungs and their draining lymph nodes. However, low levels of JSRV expression in non-respiratory tissues could have been masked by co-amplification of endogenous JSRV-related sequences, which were differentiated from JSRV by the lack of a Scal restriction site in the PCR product. To further investigate the pathogenesis of SPA, an exogenous virus-specific hemi-nested PCR was developed utilizing primers in the U3 region of JSRV LTR, where major differences between endogenous and exogenous sequences exist. This technique was shown to be > or = 10(5)-fold more sensitive than the previous gag PCR/ScaI digestion method. Using this new assay the tissue distribution of JSRV in sheep with natural and experimentally induced SPA was analysed. Proviral DNA and JSRV transcripts were found in all tumours and lung secretions of SPA-affected sheep (n = 22) and in several lymphoid tissues. The mediastinal lymph nodes draining the lungs were consistently demonstrated to be infected by JSRV (10/10). JSRV transcripts were also detected in spleen (7/9), thymus (2/4), bone marrow (4/8) and peripheral blood mononuclear cells (3/7). Proviral DNA was also detected in these tissues although in a much lower proportion of cases. JSRV was not detected in 27 samples from unaffected control animals (n = 15).
The sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. The genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type B and D oncoviruses. Enzootic nasal tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.
Sheep pulmonary adenomatosis (SPA) is a contagious and experimentally transmissible lung cancer of sheep resembling human bronchiolo-alveolar carcinoma. A type D retrovirus, known as jaagsiekte sheep retrovirus (JSRV), has been associated with the etiology of SPA, but its exact role in the induction of the tumor has not been clear due to the lack of (i) a tissue culture system for the propagation of JSRV and (ii) an infectious JSRV molecular clone. To investigate the role of JSRV in the etiology of SPA, we isolated a full-length JSRV proviral clone, pJSRV21, from a tumor genomic DNA library derived from a natural case of SPA. pJSRV21 was completely sequenced and showed open reading frames in agreement with those deduced for the original South African strain of JSRV. In vivo transfection of three newborn lambs by intratracheal inoculation with pJSRV21 DNA complexed with cationic lipids showed that pJSRV21 is an infectious molecular clone. Viral DNA was detected in the peripheral blood mononuclear cells (PBMCs) of the transfected animals by a highly sensitive JSRV-U3 heminested PCR at various time points ranging from 2 weeks to 6 months posttransfection. In addition, proviral DNA was detected in the PBMCs, lungs, and mediastinal lymph nodes of two lambs sacrificed 9 months posttransfection, but no macroscopic or histological SPA lesion was induced. We prepared JSRV particles by transient transfection of 293T cells with a JSRV construct (pCMV2JS21) in which the upstream U3 was replaced with the cytomegalovirus early promoter. Four newborn lambs were inoculated with JSRV21 particles produced in this manner, and two of them showed the classical signs of SPA 4 months postinfection. The resulting tumors were positive for JSRV DNA and protein. Thus, JSRV21 is an infectious and pathogenic molecular clone and is necessary and sufficient to induce sheep pulmonary adenomatosis.
Lentivirus infections in small ruminants represent an economic problem affecting several European countries with important sheep-breeding industries. Programs for control and eradication of these infections are being initiated and require reliable screening assays. This communication describes the construction and evaluation of a new serological screening enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to maedi-visna virus (MVV) in sheep and to caprine arthritis encephalitis virus (CAEV) in goats. The solid phase is sensitized with a combination of the major core protein p25 of MVV produced in Escherichia coli and a peptide derived from the immunodominant region of the viral transmembrane protein gp46. The peptide carries an N-terminal biotin residue and is complexed with streptavidin prior to being coated. The new assay was evaluated with 2,336 sheep serum samples from different European countries with large differences in the levels of prevalence of MVV infections, and the results have been compared to those of the standard agar gel immunodiffusion test. Discrepant samples were analyzed by Western blotting with viral lysate, and most sera could be classified unambiguously. The estimated overall sensitivity of the new ELISA was 99.4% (95% confidence interval [CI], 98.4 to 99. 8%) and the specificity was 99.3% (95% CI, 98.7 to 99.6%). A limited set of goat sera (n = 212) was also analyzed, with similar results. These data indicate that the new assay is a reliable tool that can be used in control and eradication programs for small ruminant lentivirus infections.
Sheep pulmonary adenomatosis (SPA) is a contagious lung tumour of sheep and, rarely, goats which manifests itself clinically as a progressive pneumonia. Two secretory epithelial cells are transformed, the type II pneumocyte in the alveolus and the cell of Clara in the terminal bronchiole. SPA is the most common tumour of sheep and occurs in many countries. Within affected flocks, it is estimated that SPA occurs in up to 30% of the sheep and is responsible for 50% of the mortality.
Zusammenfassung
Bei der spontanen Lungenadenomatose des Schafes (sLAS) sind histologisch häufig Rundzellinfiltrate und fibroplastische Prozesse im Lungengerüst feststellbar. Sie nehmen mit Ausdehnung des Tumors an Stärke zu. Da sie jedoch nicht immer nachweisbar sind, können sie nicht als obligate Tumorkomponente angesehen werden, sondern als mögliche Folge unspezifischer Abwehrreaktionen. In mehr als der Hälfte der Fälle ist eine meist kleinherdige myxomatöse Umwandlung des Tumorstromas nachweisbar. Daneben kommen myxomatöse Knötchen, z. T. mit Zystenbildung, zur Beobachtung, die als mesenchymale Mischkomponente der Lungenadenomatose gewertet werden.
Summary
The morphology of spontaneous pulmonary adenomatosis in sheep I. Histological findings on the tumour stroma
In spontaneous pulmonary adenomatosis of sheep there are frequently demonstrable histologically round cell infiltrations and fibroplastic processes in the lung stroma. They increase with increasing growth of the tumour. Since, however, they are not always demonstrable, they cannot be regarded as obligate tumour components but rather as possible sequelae of non‐specific defence reactions. In more than half the cases there are nodular foci of transformation of the tumour stroma which take the form of myxomatous nodules, sometimes with cyst formation, which can be seen as mesenchymatous mixed components of pulmonary adenomatosis.
Résumé
Morphologie de l'adénomatose pulmonaire spontanée du mouton I. Résultats histologiques sur le stroma tumoral
Des infiltrations de cellules rondes et des processus fibroplastiques sont souvent observés histologiquement dans le tissu de soutien du poumon lors de l'adénomatose pulmonaire spontanée du mouton. Ils augmentent avec l'éten due de la tumeur. Nétant pas toujours observables, ils ne doivent pas être considérés comme des composants tumoraux obligatories mais comme la conséquence possible de réactions de défense non spécifiques. Dans plus de la moitié des cas, on a remarqué une transformation myxomateuse en petits foyers du stroma tumoral. On a observé en plus des nodules myxomateux, en partie avec une formation tumorale, qui furent jugés comme des composants mésenchymateux mixte de l'adénomatose pulmonaire.
Resumen
Morfología de la adenomatosis pulmonar espontánea de la oveja I. Hallazgos histopatológicos en el estroma tumoral
En la adenomatosis pulmonar espontánea de la oveja (APOe) se aprecian histopatológicamente, con frecuencia, infiltraciones de células redondas y procesos fibroplásticos en el armazón pulmonar. Aumentan de espesor al proliferar el tumor. Puesto que no siempre son identificables, no se pueden considerar como componentes tumorales obligados, sino como consecuencia posible de reacciones inespecíficas de defensa. En más de la mitad de los casos se puede identificar una transformación mixomatosa, casi siempre micro‐focal, del estroma tumoral. Al lado de esto, se hallan nódulos mixomatosos, en parte con formación de quistes, interpretándose como componente mesen‐quimatosa mixta de la adenomatosis pulmonar.
Summary Jaagsiekte, a contagious lung tumour of sheep, was induced within 3–6 weeks in day-old lambs by intratracheal inoculation of SPA lung fluids concentrated by centrifugation. Electronmicroscopic examination of the tumour revealed retrovirus particles whose morphogenesis and morphology support biophysical and immunological findings that suggest a relationship with type B and type D retroviruses.
At head of title: Instituto de Estudios Turolenses de la Excma. Diputación Provincial de Teruel, adscrito al Consejo Superior de Investigaciones Científicas. Tesis--Zaragoza, 1964. Bibliography: p. 157-161. Summary in English, French, German and Spanish.
Two microimmunodiffusion tests (MIDT) for detection and measurement of ovine progressive pneumonia antibody are described. Substrates of various salt concentrations and pH were used to determine the optimal conditions for the tests. In comparisons between two MIDT and one macroimmunodiffusion test, sera from cull ewes were used. The MIDT require less reagents and were more responsive than the macroimmunodiffusion test. After extended incubation of the test materials, results in all three tests were comparable.
Lung carcinoma of sheep (Jaagsiekte) is a bronchiolar-alveolar cell carcinoma. Differences in the ultrastructural patterns of early and advanced lesions of the disease are described. A-type and C-type viruses were observed in advanced tumors and were absent in early lesions. Numerous microtubules were characteristic in the epithelial tumor cells of the early lesions and were absent in the advanced tumor. In comparison to the early lesions, extensive cytosome production, surfactant secretion, and glycogen accumulation were observed in the advanced tumor. The immune response to the early tumor lesion was restricted to the peribronchiolar lymph aggregates, while in the advanced stages of the disease the systemic immune response was markedly increased.
The transmission of maedi-visna (MV) virus was studied within two groups of sheep, one of which was also affected with sheep pulmonary adenomatosis (SPA). Serological monitoring of sheep kept in contact with both groups indicated that MV virus replication occurred to a greater extent in the group with both diseases, three of five in-contact sheep being seropositive after 1 year's exposure compared with none of six held with MV-virus-only infected lambs.
Seventeen cases of metastasis in pulmonary adenomatosis in sheep are described and histologically classified. In 6 animals there were extrathoracic lesions and in 16 the lesions were intrathoracic. Five animals showed lesions both within and outside the thorax.The extrathoracic metastases were either solid cystic neoplasias and the intrathoracic cases were either adenomatous, fibrous or mixed (scirrhous).In view of the above findings it is proposed that pulmonary adenomatosis of the lung in sheep be called carcinoma of the lung.
A preparation of ovine adenomatous lung produced clinical pulmonary adenomatosis in seven out of ten sheep inoculated intratracheally. They showed dyspnoea, occasional cough and watery discharge through the nostrils in varying degrees. The earliest symptoms occurred 150 days after inoculation. Typical adenomatous lesions ranging from the earliest foci located in “centres” of thickened interalveolar septa to sheets of cuboidal and columnar cells were observed. An eighth sheep also had gross adenomatous lesions but no typical symptoms 120 days after infection. Neither fibroplasia, lymphoreticular hyperplasia, nor metastasis to regional lymph nodes were encountered. The results of this work support the view held by other workers that sheep pulmonary adenomatosis is a transmissible lung tumour. It can be differentiated from the many adenomatoid lung lesions described in other conditions and mistakenly referred to as pulmonary adenomatosis.
Jaagsiekte (ovine pulmonary adenomatosis) was transmitted to new-born lambs by inoculation of the microsomal fraction of a cytoplasmic extract of cultured tumour cells or tumour tissue. Various treatments of the biologically active fraction were carried out to differentiate between various classes of possible aetiological agents. The results obtained suggested the involvement of a membrane-associated RNA containing virus. Reverse transcriptase activity dependent on Mg++ was subsequently demonstrated in these extracts and in lung exudate, and was shown to be associated with particles banding at a density 1,175 in sucrose gradients. These characteristics, as well as the appearance of the particles in the electron microscope, are similar to those reported for Type B and Type D retroviruses. Serial transmissions of jaagsiekte over a number of years, using cytoplasmic extracts and purified virus, strongly suggest that this virus is the aetiologic agent of jaagsiekte.
The infective agent of jaagsiekte was shown to be present in the fluid which accumulates in the respiratory tract of sheep during the terminal stages of the disease. The fluid also contained reverse transcriptase (RT) activity which showed a clear preference for a ribonucleic acid synthetic template over the corresponding deoxyribonucleic acid template and which utilised the RT specific template/primer poly (2'-0-methylcytidylate) oligodeoxyguanylate. This enzyme activity was associated with a particle which had typical retroviral buoyant densities in a range of gradient media.
A scanning electron microscopy (SEM) and transmission electron microscopy (TEM) study was made of lesions from acute, experimentally induced cases of jaagsiekte. In the SEM study tumour cells were easily identified by the abundant microvilli on their peripheral surface. The SEM study gave further insight into the development of lesions and the spatial relationship of cells involved in jaagsiekte. TEM revealed that the tumour cells were in a state of rapid protein synthesis and had many characteristics in common with other malignant cells.
In two experiments, 18 specific-pathogen free (SPF) lambs were inoculated by several routes with the Scottish strain of caprine herpesvirus 1 (CHV1). Seventeen of the lambs developed interstitial changes in the lungs ranging from focal cellular infiltration to a widespread proliferative pneumonia.
Five weeks after the initial inoculation 3 lambs were given a course of corticosteroid by intravenous injection. Subsequently virus was reisolated from all 3 lambs. Virus was also recovered from one of these lambs on one occasion prior to steroid treatment.
It has therefore been established that CHV1 can cause pneumonia and can be reisolated from infected sheep for at least 6 weeks after infection. It is suggested that CHV1 might cause a latent infection in sheep which is reactivated following the development of pulmonary adenomatosis.
Following the discovery that a flock of sheep in England was infected with the virus of maedi-virus, several seropositive sheep were brought to the Central Veterinary Laboratory and kept isolated and under observation for up to three years before being further examined at necropsy. Meanwhile, sheep in the infected flock which died or were culled were examined after death for evidence of the actual disease. At necropsy pulmonary disease was a common (although not always the sole) finding, the lesions being mostly chronic pasteurellosis and pulmonary adenomatosis. One of the 45 carcases examined showed classical lesions of advanced maedi. In four others, early or incipient lesions of maedi were found in otherwise normal lungs, while in three more, maedi was coincidental with the other pulmonary diseases. No clinical evidence to suggest maedi, other than emaciation, was seen in any of the sheep with lesions of the disease.
Morphologic features of 8 cases of sheep pulmonary adenomatosis in the United States are described. All cases were studied by light microscopy and 1 case, by electron microscopy. The common finding in all sheep was an adenoma composed of fetal type II alveolar epithelial cells. The stroma closely resembled interalveolar septa in most areas. In other areas, there was excessive collagenous or myxomatous tissue. Metastatic tumor in mediastinal lymph nodes of 2 sheep closely resembled tumor in the lung. A virus with cultural and structural characteristics like those of ovine progressive pneumonia virus was isolated from the lungs of 1 sheep, but neither virions nor viral inclusions were seen in the pulmonary parenchyma.
Between 1982 and 1991, 159 sheep suffering from chronic respiratory disease were subjected to clinical, pathological, histopathological and serological examination. Maedi was diagnosed in 82 sheep and sheep pulmonary adenomatosis (SPA) in another 59. Forty-one of the latter (69.5 per cent) were seropositive for maedi-visna (MV) virus infection, but only six (10.2 per cent) showed concurrent lung lesions of maedi. Even disregarding the MV seronegative sheep and those younger than two years old, the rate of concurrent maedi lesions did not exceed 18 per cent. During a similar period, 5060 sheep from 161 flocks (86 of which also provided the 159 affected animals) were tested for antibodies to MV virus. The average seroprevalence of MV virus infection among flocks in which SPA was detected was 66.4 per cent, whereas in those in which SPA could not be demonstrated, and in those in which necropsies were not performed, the levels of MV virus infection were 55.1 per cent and 43.6 per cent, respectively. The effect of SPA on the seroprevalence of MV virus infection was independent of other factors, such as breed of sheep or the size of the flocks. These results provide evidence that SPA plays a role in the spread of MV virus infection, although a synergistic effect of the simultaneous infection on the expression of concurrent lesions does not seem to occur.
Clinical pulmonary ad-adenomatosis of sheep ( jaagsiekte) Journal of Com-enomatosis of sheep produced experimentally
- Histological
Histological patterns of the metastases in pulmonary Wandera, J. G. (1970). Clinical pulmonary ad-adenomatosis of sheep ( jaagsiekte). Journal of Com-enomatosis of sheep produced experimentally. British Veterinary Journal, 126, 185–193.
Right lung showing a solitary tumour nodule in the ventral part of the diaphragmatic lobe. Fig
- Atypical
- Spa
Atypical SPA. Right lung showing a solitary tumour nodule in the ventral part of the diaphragmatic lobe. Fig.
and B retrovirus of sheep and goats Microimmunodiffusion test for ovine Virology
- L D Winward
- L Leendersten
- D Shen
Winward, L. D., Leendersten, L. and Shen, D. and B retrovirus of sheep and goats. Journal of T. (1979). Microimmunodiffusion test for ovine Virology, 66, 4930–4939.
Estudios sobre la ad De las Heras, M. enomatosis pulmonar ovina en Españ a Jaagsiekte sheep retrovirus is Universidad de Zaragoza. Instituto de Estudios necessary and sufficient to induce a contagious lung Turolenses-CSIC, Ed, Teruel. cancer of sheep
- D Dualde-Pé
- M Palmarini
- J M Sharp
- H Fan
Dualde-Pé, D. (1966). Estudios sobre la ad-Palmarini, M., Sharp, J. M., De las Heras, M. enomatosis pulmonar ovina en Españ a. Ph.D. Thesis, and Fan, H. (1999). Jaagsiekte sheep retrovirus is Universidad de Zaragoza. Instituto de Estudios necessary and sufficient to induce a contagious lung Turolenses-CSIC, Ed, Teruel. cancer of sheep. Journal of Virology, 73, 6964–6972.
carcinoma ( jaagsiekte) of sheep Rapid transmission of sheep study of early and advanced tumour lesions. American pulmonary adenomatosis ( jaagsiekte) in young
- I Hod
- A Herz
- A Zimber
- Pulmonary
- J M Sharp
- K W Angus
- E W Gray
- Scott
Hod, I., Herz, A. and Zimber, A. (1977). Pulmonary Sharp, J. M., Angus, K. W., Gray, E. W. and Scott, carcinoma ( jaagsiekte) of sheep. Ultrastructural F. M. M. (1983). Rapid transmission of sheep study of early and advanced tumour lesions. American pulmonary adenomatosis ( jaagsiekte) in young Journal of Pathology, 86, 545–557.
Sheep Herring, A Further evidence for a epidemiological aspects In: Developments in Veterinary retrovirus as the aetiological agent of sheep pul-Virology: Maedi-Visna and Related Diseases, G. Pé monary adenomatosis ( jaagziekte). Veterinary Micro-and
- J M Sharp
- K W J Angus
- J M Sharp
- F M M Scott
- K W Pulmonary Adenomatosis Angus
Sharp, J. M. and Angus, K. W. (1990). Sheep Herring, A. J., Sharp, J. M., Scott, F. M. M. and pulmonary adenomatosis: clinical, pathological and Angus, K. W. (1983). Further evidence for a epidemiological aspects. In: Developments in Veterinary retrovirus as the aetiological agent of sheep pul-Virology: Maedi-Visna and Related Diseases, G. Pé monary adenomatosis ( jaagziekte). Veterinary Micro-and R. Hoff Jørgensen, Eds, Kluwer Academic biology, 8, 237–249.
Infection of specific-pathogen I. and Saez De Ocariz Pathological and free lambs with a herpesvirus isolated from pul-epidemiological aspects of the coexistence of maedi-monary adenomatosis
- F M M Scott
- J M Sharp
- K W Angus
- L Gonzá
- R A Juste
- L A Cuervo
- Idigoras
- E W Gray
Scott, F. M. M., Sharp, J. M., Angus, K. W. and Gonzá, L., Juste, R. A., Cuervo, L. A., Idigoras, Gray, E. W. (1984). Infection of specific-pathogen I. and Saez De Ocariz, C. (1993). Pathological and free lambs with a herpesvirus isolated from pul-epidemiological aspects of the coexistence of maedi-monary adenomatosis. Archives of Virology, 80, 147– visna and sheep pulmonary adenomatosis. Research 162. in Veterinary Science, 54, 140–146.
A new sensitive Gonzá El Maedi o neumoní progresiva serological assay for detection of lentivirus infections en el conjunto de las enfermedades respiratorias in small ruminants
- E Saman
- Van Eynde
- G Lujan
- L Extramiana
- Package
- Version
- B Madison
- G Harkiss
- F Tolari
- L Gonzá
- Amorena
- B Wisconsin
- N Watt
- J Badiola
Genetics Computer Group (1994). Program manual Saman, E., Van Eynde, G., Lujan, L., Extramiana, for the Wisconsin package, Version 8. Madison, B., Harkiss, G., Tolari, F., Gonzá, L., Amorena, Wisconsin. B., Watt, N. and Badiola, J. (1999). A new sensitive Gonzá, L. (1990). El Maedi o neumoní progresiva serological assay for detection of lentivirus infections en el conjunto de las enfermedades respiratorias in small ruminants. Clinical and Diagnostic Laboratory cró nicas del ganado ovino en la Comunidad Au-Immunology, 6, 734–740.
Pulmonary adenomatosis Aetiology of jaagsiekte: transmission siekte) in sheep with special reference to its oc-by means of subcellular fractions and evidence for currence in Israel
- D W Verwoerd
- A N Williamson
- De Villiers
- T A Nobel
Verwoerd, D. W., Williamson, A. N. and De Villiers, Nobel, T. A. (1958). Pulmonary adenomatosis ( jaag-E. M. (1980). Aetiology of jaagsiekte: transmission siekte) in sheep with special reference to its oc-by means of subcellular fractions and evidence for currence in Israel. Refuah Veterinarith, 15, 98–101.
the involvement of a retrovirus
- T A Neumann
- F Klopfer
the involvement of a retrovirus. Onderstepoort Journal Nobel, T. A., Neumann, F. and Klopfer, U. (1969).
Zur Morphologie der Spontanen Dahlberg Lesions Lungenadenomatose des Schafes. 1. Histologische and retroviruses associated with naturally occurring Befunde am Tumorstroma. Zentralblatt fü Vet-ovine pulmonary carcinoma (sheep pulmonary ad-erinä
- R H Rosadio
- J M Sharp
- M D Lairmore
- O Geisel
Rosadio, R. H., Sharp, J. M., Lairmore, M. D., Geisel, O. (1975). Zur Morphologie der Spontanen Dahlberg, J. E. and DeMartini, J. C. (1988). Lesions Lungenadenomatose des Schafes. 1. Histologische and retroviruses associated with naturally occurring Befunde am Tumorstroma. Zentralblatt fü Vet-ovine pulmonary carcinoma (sheep pulmonary ad-erinä, B-22, 535–543.
Adenomatosis pulmonar ovina (jaagsiekte): células que infiltran el tumor y modificaciones en ganglios linfáticos regionales
- De las Heras
Sheep pulmonary adenomatosis (jaagsiekte) in slaughtered sheep. Variation in pathological characteristics
- De las Heras
Epizootic adenomatosis in the lungs of sheep. Comparisons with jaagsiekte, verminous pneumonia and progressive pneumonia
- Dungal
El Maedi o neumonı́a progresiva en el conjunto de las enfermedades respiratorias crónicas del ganado ovino en la Comunidad Autónoma Vasca
- L González