Endogenous betaretroviruses of sheep: teaching new lessons in retroviral interference and adaptation

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Abstract
The endogenous betaretroviruses of small ruminants offer an excellent model to investigate the biological relevance of endogenous retroviruses (ERVs). Approximately twenty copies of endogenous betaretroviruses (enJSRVs) are present in the genome of sheep and goats. enJSRVs are highly related to Jaagsiekte sheep retrovirus (JSRV) and the Enzootic nasal tumour virus (ENTV), the causative agents of naturally occurring carcinomas of the respiratory tract of sheep. enJSRVs interact/interfere at different levels both with the host and with their exogenous and pathogenic counterparts. enJSRVs blocks the exogenous JSRV replication by a novel two-step interference mechanism acting both early and late during the virus replication cycle. enJSRVs are highly active, they are abundantly and specifically expressed in the epithelium of most of the ovine female reproductive tract. The specific spatial and temporal expression of enJSRVs supports a role in trophoblast development and differentiation as well as conceptus implantation. In addition, enJSRVs are expressed during fetal ontogeny leading to the apparent tolerance of sheep towards the pathogenic JSRV. Thus, the sheep/enJSRVs system is a model that can be utilized to study many different aspects of ERVs and retrovirus biology. The impressive technologies developed to study the sheep reproductive biology, in conjunction with the knowledge gained on the molecular biology of enJSRVs, makes the ovine system an ideal model to design experiments that can functionally address the role of ERVs in mammalian physiology.