Life History of the Oldest Lentivirus: Characterization of ELVgv Integrations in the Dermopteran Genome

Abstract

Endogenous retroviruses are genomic elements formed by germline infiltration by originally exogenous viruses. These molecular fossils provide valuable information about the evolution of the retroviral family. Lentiviruses are an extensively studied genus of retroviruses infecting a broad range of mammals. Despite a wealth of information on their modern evolution, little is known about their origins. This is partially due to the scarcity of their endogenous forms. Recently, an endogenous lentivirus, ELVgv, was discovered in the genome of the Malayan colugo (order Dermoptera). This represents the oldest lentiviral evidence available and promises to lead to further insights into the history of this genus. In this study, we analyzed ELVgv integrations at several genomic locations in four distinct colugo specimens covering all the extant dermopteran species. We confirmed ELVgv integrations in all the specimens examined, which implies that the virus originated before the dermopteran diversification. Using a locus-specific dermopteran substitution rate, we estimated that the proviral integrations occurred 21-40 Ma. Using phylogenetic analysis, we estimated that ELVgv invaded an ancestor of today's Dermoptera in an even more distant past. We also provide evidence of selective pressure on the TRIM5 antiviral restriction factor, something usually taken as indirect evidence of past retroviral infections. Interestingly, we show that TRIM5 was under strong positive selection pressure only in the common dermopteran ancestor, where the ELVgv endogenization occurred. Further experiments are required to determine whether ELVgv participated in the TRIM5 selection.

Prisoners of war — host adaptation and its constraints on virus evolution

“…The endogenous lentiviruses in rabbits 45 integrated over 12 million years (myr) ago on the basis of the presence of unambiguous orthologous copies of this virus in lapine species that diverged after this time 91 . Integration times calculated for endogenous lentiviruses detected in ferrets, lemurs and colugos further demonstrate the circulation of lentiviruses in the range of tens of millions of years [46][47][48] .…”

“…For example, lentiviruses were originally considered as a recently emerged group of viruses on the basis of the very recent origins of HIV-1 itself and measured substitution rates that place the origins of lentiviruses to a few thousand years ago 21 . However, endogenous lentiviruses in rabbits 45 , ferrets, Madagascan lemurs and colugos demonstrate the circulation of lentiviruses over almost the entire time span of mammalian evolution [46][47][48] . In addition to retroviruses, other RNA and DNA viruses have also adventitiously integrated into host germ lines and created records of ancient infections.…”

Retroviruses drive the rapid evolution of mammalianAPOBEC3genes

“…This raises the possibility that Vif-like proteins encoded by ancestral retroviruses and/or ERVs may have exerted diversifying selective pressure on A3s. Indeed, remnants of vif genelike ORFs have been identified in endogenous lentiviruses (43)(44)(45). In addition, it has recently been reported that herpesviruses encode ribonucleotide reductase large subunits that degrade human A3 proteins (5,46,47) and that the A3 antagonists of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus specifically recognize the loop 7 structure of A3B (5).…”

The Expectations and Challenges of Wildlife Disease Research in the Era of Genomics: Forecasting with a Horizon Scan-like Exercise

“…Commonly referred to as viral "fossils," EVEs provide critical sequences for calibrating or informing viral phylogenies (Aiewsakun and Katzourakis 2015). One of the best examples is the discovery of lentiviral EVEs in various mammalian genomes, pushing back the evolutionary origins of lentiviruses at least 60 million years (Hron et al 2016).…”