Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

Abstract

Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

HERV-K–specific T cells eliminate diverse HIV-1/2 and SIV primary isolates

“…A precedent exists in mice for the mobilization of endogenous retroviruses by exogenous retroviruses, where infection with exogenous ectopic MuLV has been shown to result in the replication of defective endogenous polytopic retroviruses (34). This has led to the suggestion that periods of replication of endogenous retroviruses in the mouse have been initiated by exogenous retroviruses capable of circumventing restriction factors.…”

Pragmatic turn in biology: From biological molecules to genetic content operators

“…During reverse transcription the reverse transcriptase switches between two or more templates, generating a new DNA sequence [60] . Similar sequence generations are known in various co-infection events such as the combination of external RNA viruses and persistent endogenous retrovirus, infectious RNA viruses with former viruses, retaining defective parts which can be combined into new sequence orders of still functioning viruses [52,53] . Interestingly, not only viruses generate de novo, or combine and recombine sequences.…”

“…This change in perspective from molecules to agentbased behaviour will look at interactions of RNA viruses, DNA viruses, RNA-DNA viruses, viral swarms, and sub-viral groups like any ligated RNA stem loop groups that cooperate and coordinate (regulate) within cellular genomes as replication-relevant co-players [51][52][53] . Or they interact as suppression-relevant silencers or as infectionderived modular tools of non-coding RNAs that have built consortia of complementary agents that function together such as retrovirus-derived remnants, such as LTRs, non-LTRs, group Ⅱ introns, rRNAs, tRNAs, spliceosomes, editosomes, and other counterbalancing modules [54][55][56][57][58] .…”

A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains

“…Strikingly, defective elements carrying different inactivating mutations or even large deletions can be often mobilized in trans by active copies (Mager and Freeman 2000;Horie et al 2007;Ribet et al 2008a). The transferred sequences can even be packaged into virions released from the newly infected cells (Evans et al 2009). …”