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Background: Porcine 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., Results: Phylogenetic 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., Conclusions: Evidence 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.

Diversity of long terminal repeats (LTRs) from γ1 endogenous retroviruses (ERVs) was analysed by DNA sequencing in 10 species of the family Suidae (suids, pigs and hogs). Phylogenetic analysis separated LTR sequences into two groups which correlated approximately with either the previously described cluster I and III, or the clusters II, IV and V. Interestingly, a specific LTR exhibiting a novel molecular rearrangement was identified exclusively within African host species when compared to LTRs previously reported from known ERVs in the domestic pig (Sus scrofa). Furthermore, other sections of LTRs appear to be unique to African suids as suggested by phylogenetic analysis. These differences between African and Eurasian ERV lineages show that these ERVs belong to different viral sub-populations, implying coevolution of endogenous viral sequences with their host species and providing no evidence of transfer of viral sequences between African and Eurasian suids., (Copyright © 2011 Elsevier B.V. All rights reserved.)