North American Big Brown Bats (Eptesicus fuscus) Harbor an Exogenous Deltaretrovirus (2020)

Bats are the reservoir for a large number of zoonotic viruses, including members of <i>Coronaviridae</i> (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), <i>Paramyxoviridae</i> (Hendra and Nipah viruses), <i>Rhabdoviridae</i> (rabies virus), and <i>Filoviridae</i> (Ebola virus) as exemplars. Many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. Here, viral metagenomic sequencing of samples from bats submitted for rabies virus testing, largely due to human exposure, identified a novel, highly divergent exogenous <i>Deltaretrovirus</i> from a big brown bat (<i>Eptesicus fuscus</i>) in South Dakota. The virus sequence, corresponding to <i>Eptesicus fuscus</i> deltaretrovirus (EfDRV), comprised a nearly complete coding region comprised of canonical 5'-<i>gag</i>-<i>pro</i>-<i>pol</i>-<i>env</i>-3' genes with 37% to 51% identity to human T-lymphotropic virus (HTLV), an infectious retrovirus that causes T-cell lymphoma. A putative <i>tax</i> gene with 27% identity to HTLV was located downstream of the <i>pol</i> gene along with a gene harbored in an alternative reading frame which possessed a conserved domain for an Epstein-Barr virus nuclear antigen involved in gene transactivation, suggesting a regulatory function similar to that of the deltaretrovirus <i>rex</i> gene. A TaqMan reverse transcriptase PCR (RT-PCR) targeting the <i>pol</i> gene identified 4/60 (6.7%) bats as positive for EfDRV, which, combined with a search of the <i>E. fuscus</i> genome that failed to identify sequences with homology to EfDRV, suggests that EfDRV is an infectious exogenous virus. As all known members of <i>Deltaretrovirus</i> can cause malignancies and <i>E. fuscus</i> is widely distributed in the Americas, often with a colonial roosting behavior in human dwellings, further studies are needed to investigate potential zoonosis.<b>IMPORTANCE</b> Bats host a large numbers of viruses, many of which are zoonotic. In the United States, the big brown bat (<i>Eptesicus fuscus</i>) is widely distributed and lives in small colonies that roost in cavities, often in human dwellings, leading to frequent human interaction. Viral metagenomic sequencing of samples from an <i>E. fuscus</i> bat submitted for rabies testing identified the first exogenous bat <i>Deltaretrovirus</i> The <i>E. fuscus</i> deltaretrovirus (EfDRV) genome consists of the typical deltaretrovial 5'-<i>gag</i>-<i>pro</i>-<i>pol</i>-<i>env</i>-3' genes along with genes encoding two putative transcriptional transactivator proteins distantly related to the Tax protein of human T-cell lymphotrophic virus and nuclear antigen 3B of Epstein-Barr virus. Searches of the <i>E. fuscus</i> genome sequence failed to identify endogenous EfDRV. RT-PCR targeting the EfDRV <i>pol</i> gene identified 4/60 (6.7%) bats with positive results. Together, these results suggest that EfDRV is exogenous. As all members of <i>Deltaretrovirus</i> are associated with T- and B-cell malignancies or neurologic disease, further studies on possible zoonosis are warranted.