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.
Highlights
Endogenous retroviruses (ERVs) represent a class of retroviruses that are inherited through the germline of their hosts like cellular genes
Two main hypotheses have been proposed to understand the maintenance of the coding capacities of ERVs: (1) endogenous retroviral proteins are necessary for the replication of ERVs, and (2) endogenous retroviral proteins are beneficial to their hosts
Our first aim was to estimate the number of enJSRV proviruses coding the W21 Gag variant relative to the number of wild-type (R21) enJSRV proviruses
Summary
Endogenous retroviruses (ERVs) represent a class of retroviruses that are inherited through the germline of their hosts like cellular genes. ERVs represent a significant portion of the host genomes (i.e., 8% of the human genome) and are generally inactivated by point mutations and/or indels [1]. Some of these endogenous retroviruses still encode functional retroviral proteins. One well-illustrated beneficial impact of ERVs concerns the protection of the host from infection by related exogenous retroviruses. Protection can occur later during the replication cycle of the retrovirus, either before the integration of the retroviral genome into the host nucleus [3] or during the assembly of the retroviral particles [4]
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