Evolution of endogenous retroviruses in the Suidae: evidence for different viral subpopulations in African and Eurasian host species

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.

Epigenetic marking and repression of porcine endogenous retroviruses

“…The coding regions within PERV-c1 and PERV-b3 elements were mainly intact with only few premature stop codons (Fig. 1a, c) whereas, in accordance with a previous study (Nascimento et al, 2011), the majority of the PERV-c2 coding regions were disrupted by numerous premature stop codons (Fig. 1b).…”

Strong purifying selection in endogenous retroviruses in the saltwater crocodile (Crocodylus porosus) in the Northern Territory of Australia

“…This leads to a collection of proviruses that show high levels of nucleotide and amino acid diversity while at the same time retaining the original sequence characteristics, as seen in this study. This level of sequence diversity is not uncommon for ERVs, and is comparable to what has been observed in mammalian ERVs [31,32]. …”

Promoter activity analysis and methylation characterization of LTR elements of PERVs in NIH miniature pig

“…Recently, evidence has been obtained regarding the presence of at least 2 viral subpopulations in gamma1 retroviruses from Eurasian and African host species (Nascimento et al, 2011). These evolutionary occurrences of viral recombination may be relevant to xenotransplantation risk analysis since these recombinants could favor adaptation and confer the capacity to maintain ongoing infection in somatic cells and germ cells (Nascimento et al, 2011).…”

“…These evolutionary occurrences of viral recombination may be relevant to xenotransplantation risk analysis since these recombinants could favor adaptation and confer the capacity to maintain ongoing infection in somatic cells and germ cells (Nascimento et al, 2011). Thus, like this study also should be taken into account in xenotransplantation.…”