Jaagsiekte Sheep Retrovirus (JSRV): From virus to lung cancer in sheep

Université de Lyon 1, INRA, UMR754, Ecole Nationale Vétérinaire de Lyon, IFR 128, F-69007, Lyon, France.
Veterinary Research (Impact Factor: 2.82). 03/2007; 38(2):211-28. DOI: 10.1051/vetres:2006060
Source: PubMed


Jaagsiekte Sheep Retrovirus (JSRV) is a betaretrovirus infecting sheep. This virus is responsible for a pulmonary adenocarcinoma, by transformation of epithelial cells from the bronchioli and alveoli. This animal cancer is similar to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral aetiology has not yet been identified. JSRV interacts with target cells through the membrane receptor Hyal2. The JSRV genome is simple and contains no recognised oncogene. It is now well established that the viral 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 in the envelope-induced transformation. Tumour development is associated with telomerase activation. This review will focus on the induction of cancer by JSRV.

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    • "Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer in sheep caused by Jaagsiekte sheep retrovirus (JSRV), a member of the genus Betaretrovirus (Leroux et al. 2007). Transmission occurs mainly via the respiratory route, causing a lifelong chronic infection which may eventually lead to clinical pathology (Palmarini & Fan 2001; Caporale et al. 2005). "
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    ABSTRACT: Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer in sheep caused by Jaagsiekte sheep retrovirus (JSRV). OPA is present in many sheep-rearing countries causing economic and welfare issues, as currently no efficient vaccines or treatments are available. Breed differences suggest a host genetic component may influence the pathogenesis of OPA, but so far few genes have been identified. In this work, a genetic association study was carried out in Latxa dairy sheep which were classified as cases/controls based on the presence/absence of OPA lung tumours. Candidate genes included cytokines and a receptor and innate immunity genes. After SNPs in the candidate genes were identified, the distribution of alleles in cases and controls was compared by means of logistic regression analyses at the allelic, genotypic and haplotypic levels. The association analysis showed that several candidate genes were significantly associated with resistance or susceptibility to OPA; two of the candidates, CCR5 and MX1, remained significantly associated with resistance and susceptibility respectively, even after Bonferroni correction.
    Animal Genetics 09/2015; DOI:10.1111/age.12351 · 2.21 Impact Factor
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    • "The enJSRV/exJSRV retroviruses in sheep represent a powerful model for the study of interactions between an ERV, its exogenous counterpart and their host. The sheep genome contains approximately 30 copies of the endogenous retrovirus enJSRV, which is highly related to the exogenous betaretrovirus exJSRV (90%–98% identity at the amino acid level), the etiological agent of ovine pulmonary adenocarcinoma [5]–[8]. Among the enJSRVs, it has been shown that the enJS56A1 provirus was able to block the release of infectious JSRV particles when co-expressed in cultured cells, illustrating a novel mechanism of retroviral interference [9]. "
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    ABSTRACT: The Jaagsiekte sheep retrovirus exJSRV and its endogenous counterpart enJSRV co-exist in sheep. exJSRV, a betaretrovirus, is the etiological agent of ovine pulmonary adenocarcinoma, and it has been demonstrated in vitro that an enJSRV Gag variant bearing the R-to-W amino acid change at position 21 was able to block exJSRV budding from the cells, providing a potential protective role for the host. In this work, we developed a fast mutation detection assay based on the oligo ligation assay (OLA) that permits the quantification of the relative proportions of the R21 and W21 Gag variants present in individual genomes and in cDNA obtained from normal and exJSRV-induced lung tumors. We have shown that the W21/R21 ratio is variable within and between breeds. We also describe for the first time that putative protecting enJSRV variants were expressed in alveolar type II cells (AECII), the major target of exJSRV.
    PLoS ONE 07/2012; 7(7):e41965. DOI:10.1371/journal.pone.0041965 · 3.23 Impact Factor
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    • "Ovine pulmonary adenocarcinoma is a naturally occurring lung cancer that arises in sheep infected by jaagsiekte sheep retrovirus (JSRV) [5]–[7]. It has been described for a long time as an animal model for human P-ADC, as the two tumours share strikingly similar clinical, radiological and pathological features [7], [8]. "
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    ABSTRACT: Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32-7.87, p = 0.010), never-smoker status (OR = 3.57, 95% CI: 1.27-10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10-10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05-24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.
    PLoS ONE 05/2012; 7(5):e37889. DOI:10.1371/journal.pone.0037889 · 3.23 Impact Factor
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