Abstract

BackgroundPorcine endogenous retroviruses (PERVs) represent remnants of an exogenous form that have become integrated in the domestic pig (Sus scrofa) genome. Although they are usually inactive, the capacity of γ1 ERVs to infect human cells in vitro has raised concerns about xenotransplantation because the viruses could cross the species barrier to humans. Here we have analyzed the evolution of γ1 ERVs in ten species of Suidae (suids, pigs and hogs) from Eurasia and Africa using DNA sequences for their coding domains (gag, pro/pol and env genes). For comparison with γ1 PERVs, we have also analysed γ2 ERVs which in domestic pigs are known to be inactive and do not pose a risk to xenotransplantation.ResultsPhylogenetic analysis using Bayesian inference showed that γ1 and γ2 ERVs have distinctive evolutionary histories. Firstly, two different viral lineages of γ1 ERVs were found and a coevolutionary analysis demonstrated that they correspond broadly to their host phylogeny, one of Eurasian and another of African species, and show no evidence of horizontal transmission. γ2 ERVs, however, show a bush-like evolution, suggesting a rapid viral radiation from a single common ancestor with no correspondence between host and viral evolutionary trees. Furthermore, though γ1 ERV env genes do not possess frequent stop codons, γ2 env genes do. To understand whether γ1 suid ERVs may be still replicating, we have also evaluated their likely mechanism of proliferation by statistically testing internal to terminal branches using nonsynonymous versus synonymous substitution ratios. Our results suggest that γ1 ERVs are increasing in copy number by reinfection, which requires the translocation of the virus from one cell to another.ConclusionsEvidence of at least two viral subpopulations was observed in γ1 ERVs from Eurasian and African host species. These results should be taken into account in xenotransplantation since γ1 ERVs appear to be codiverging with their host and maintaining ongoing capacity to infect somatic and germ cells.

Highlights

  • Porcine endogenous retroviruses (PERVs) represent remnants of an exogenous form that have become integrated in the domestic pig (Sus scrofa) genome

  • Screening of Endogenous retroviruses (ERVs) sequences A total of 144 partial g1 ERV sequences comprising the pol, gag and env genes and 40 g2 env were generated (Table 1)

  • No g1 ERV genes were amplified in the babirusa, while pol and env class A and C were not amplified in the forest hog, and pol and env class A were not amplified in the Javan warty pig and the desert warthog, respectively

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Summary

Introduction

Porcine endogenous retroviruses (PERVs) represent remnants of an exogenous form that have become integrated in the domestic pig (Sus scrofa) genome. They are usually inactive, the capacity of g1 ERVs to infect human cells in vitro has raised concerns about xenotransplantation because the viruses could cross the species barrier to humans. Endogenous retroviruses (ERVs) are the remnants of an exogenous viral form that infected and became integrated in germ cell genomes [1]. In the domestic pig and wild boar (Sus scrofa) genome, ERVs are referred to as PERVs (porcine endogenous retroviruses) and belong to the b and g genera comprising several viral groups [5,6]. The capacity of g1 ERVs to infect human cells in tissue culture raised serious concerns on the safety of xenotransplantations [9,10] because pigs are the first choice of xenograft donors [11,12,13]; g1 ERVs have been extensively studied in Sus scrofa

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