Host Species Barriers to Jaagsiekte Sheep Retrovirus Replication and Carcinogenesis

Abstract

f Understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. In this study, in order to further clarify the pathogenesis of OPA, we investigated whether goats are resistant to JSRV replication and carcinogenesis. We found that JSRV induces lung tumors in goats with macroscopic and histopathological features that dramatically differ from those in sheep. However, the origins of the tumor cells in the two species are identical. Interestingly, in experimentally infected lambs and goat kids, we revealed major differences in the number of virus-infected cells at early stages of infection. These differences were not related to the number of available target cells for virus infection and cell transformation or the presence of a host-specific immune response toward JSRV. Indeed, we also found that goats possess transcriptionally active endogenous retroviruses (enJSRVs) that likely influence the host immune response toward the exogenous JSRV. Overall, these results suggest that goat cells, or at least those cells targeted for viral carcinogenesis, are not permissive to virus replication but can be transformed by JSRV.

Exogenous Jaagsiekte Sheep Retrovirus type 2 (exJSRV2) related to ovine pulmonary adenocarcinoma (OPA) in Romania: prevalence, anatomical forms, pathological description, immunophenotyping and virus identification

“…The histological features of OPA consist of proliferation of epithelial cells into acini, papillary and solid structures, supported by a fibrovascular stroma. In atypical form, in addition to the epithelial neoplasia, marked fibroblast proliferation, collagen deposition and mononuclear cell infiltration are characteristic microscopic changes [41]. These inflammatory changes may be caused by intercurrent infections or a specific immune response of the host [4].…”

“Ménage à Trois”: The Evolutionary Interplay between JSRV, enJSRVs and Domestic Sheep

“…Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a naturally occurring lung cancer of sheep [ 9 ]. OPA is a common disease of sheep throughout the world, but is rarely found in goats and wild moufflons [ 10 , 11 ]. Importantly, it shares several characteristics with some forms of human lung adenocarcinomas, which makes it a fitting large animal model for lung carcinogenesis [ 12 , 13 ].…”

“…In nature, only a handful of reports have described OPA in this animal species at low incidence [ 54 , 55 , 56 , 57 ]. Experimentally, JSRV can also infect LAPCs of goat kids and lead to small tumor lesions [ 11 , 58 ]. However, available data suggest that goat cells are susceptible to viral infection but not to viral replication [ 11 ].…”

“…Experimentally, JSRV can also infect LAPCs of goat kids and lead to small tumor lesions [ 11 , 58 ]. However, available data suggest that goat cells are susceptible to viral infection but not to viral replication [ 11 ]. Interestingly, goats also harbor transcriptionally active endogenous retroviruses similar to enJSRVs that may lead to tolerance towards the exogenous JSRV [ 6 , 11 ].…”

Exploiting ovine immunology to improve the relevance of biomedical models

“…This model therefore provides an opportunity for longitudinal studies of lung cancer pathogenesis beginning with a single transformed cell through to the development of large tumours. To date, this model has mainly been used to examine aspects of virus–host interaction in OPA ( Caporale et al, 2006; Cousens et al, 2007; Caporale et al, 2013 ) but it shows great promise as a platform for future studies on lung cancer pathogenesis; for example, in developing in vivo cancer imaging methods or studying early events in tumourigenesis. This is particularly important given the poor prognosis of human lung cancer and the difficulty of studying early tumours in humans.…”