Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells

Abstract

Endogenous retroviruses (ERVs) were acquired during evolution of their host organisms after infection and mendelian inheritance in the germline by their exogenous counterparts. The ERVs can spread in the host genome and in some cases they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is one of only a few well-defined examples of evolutionarily recent invasion of mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV integration sites have been detected in wild ranging mule deer (Odocoileus hemionus) host populations. Here, we describe for the first time induction of replication competent CrERV by cocultivation of deer and human cells. We characterize the physical properties and tropism of the induced virus. The genomic sequence of the induced virus is phylogenetically related to the evolutionarily young endogenous CrERVs described so far. We also describe the level of replication block of CrERV on deer cells and its capacity to establish superinfection interference.

Existence of Two Distinct Infectious Endogenous Retroviruses in Domestic Cats and Their Different Strategies for Adaptation to Transcriptional Regulation

“…Consequently, mammalian genomes are littered with the signatures of ancient retroviral infections. Most ERVs have already been inactivated by accumulated mutations that disrupt viral genes or regulatory sequences.Although most ERVs are inactivated, a few ERVs that still retain potential replication capacities have been observed in several animals (6), including mice (7), koalas (8, 9), pigs (10-14), and mule deer (15,16). Some of these ERVs reside in the host genome as intact proviruses, while others appear to have been generated through reassortment or recombination among inactivated proviruses (17-19).…”

“…Although most ERVs are inactivated, a few ERVs that still retain potential replication capacities have been observed in several animals (6), including mice (7), koalas (8,9), pigs (10)(11)(12)(13)(14), and mule deer (15,16). Some of these ERVs reside in the host genome as intact proviruses, while others appear to have been generated through reassortment or recombination among inactivated proviruses (17)(18)(19).…”

Presence of a Shared 5′-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus

“…Because of accumulated mutations or internal recombinations that result in a solo long terminal repeat (LTR), almost all ERVs are inactivated; however, the neutralization strategies and strengths among proviruses are diverse. For example, some recently acquired ERVs retain replication competence and, therefore, can threaten host existence (8)(9)(10)(11)(12). Moreover, interactions among partially inactivated ERVs or modern viral genomes that occur through reassortment or recombination result in a rapid evolution of retroviruses, and this phenomenon can cause increasing genetic diversities or result in the serious occurrence of viral disease reemergence (13)(14)(15)(16).…”

Recombination marks the evolutionary dynamics of a recently endogenized retrovirus

“…Based on the phylogeny of several CrERV identified in the mule deer genome, at least four distinct epizootics resulted in germ line colonization (Kamath et al 2013). A full-length retrovirus representing the youngest of the CrERV lineages was recovered by co-culture on human cells, indicating that some of these CrERV are still capable of infection (Fábryová et al 2015). In this study, we expand on these preliminary data by sequencing a mule deer genome and conducting phylogenetic analyses on a majority of reconstructed CrERV genomes.…”