Article

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

ABSTRACT

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.
    Full-text · Article · Sep 2015 · Animal Genetics
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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.
    Full-text · Article · Jul 2012 · PLoS ONE
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    • "LF functions as an inhibitory agent for endothelial cell activity, induces interleukin (IL)-18 production (Shimamura et al., 2004) and enhances natural killer cell activity (Bezault et al., 1994), but the exact mechanism for the antitumour activity of LF in vivo has not yet been fully elucidated. Human BAC and OPA have a similar histological appearance, clinical presentation and behaviour (Sun et al., 2007;Leroux et al., 2007;Griffiths et al., 2010). Therefore, it is probable that OPA has a similar degree of vascularization as human BAC. "
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    ABSTRACT: Ovine pulmonary adenomatosis (OPA), also known as jaagsiekte, is a transmissible beta retrovirus-induced lung tumour of sheep that has several features resembling human bronchoalveolar carcinoma (BAC). Angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of growth factors including vascular endothelial growth factor (VEGF)-C, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-C and its receptor (PDGFR-α). Bovine lactoferrin (bLF), an iron and heparin-binding glycoprotein secreted into various biological fluids, has been implicated in innate immunity and has anti-inflammatory and anti-tumour functions. Tissues from 16 cases of OPA were compared with tissues from seven healthy control sheep by immunohistochemistry. Expression of the markers was assessed semi-quantitatively by ascribing an immunoreactivity score (IRS) with a maximum value of 300. VEGF-C, bFGF, PDGF-C, PDGFR-α and bLF signals were detected in 10/16, 15/16, 12/16, 15/16 and 10/16 of the OPA cases studied, respectively. bLF expression was weak in the neoplastic epithelial cells (IRS 21.4 ± 10.0) in contrast to high levels detected in infiltrating macrophages and plasma cells (IRS 141.3 ± 24.8 and 140.0 ± 25.1, respectively). The PDGFR-α IRS was elevated for neoplastic epithelial cells (108.9 ± 18.2) and was lowest for macrophages and plasma cells (20.4 ± 13.1 and 13.7 ± 12.4, respectively). These results suggest that bFGF, VEGF-C and PDGF-C have roles in the pathogenesis of OPA. bLF may activate macrophages and plasma cells in these lesions, but limited expression of bLF by neoplastic cells may be a consequence of defective or impaired function of this molecule.
    Full-text · Article · Jun 2012 · Journal of comparative pathology
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