Large, stable, contemporary interspecies recombination events in circulating human Herpes simplex viruses

BACKGROUND:The ubiquitous human pathogens, herpes simplex virus (HSV)-1 and HSV-2, are distinct viral species that diverged approximately 6 million years ago. At least 4 small, ancient HSV-1 × HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and nonrecombinants at each locus circulating today. However, it is unknown whether interspecies recombination can affect other loci and whether new recombinants continue to be generated. METHODS:Using 255 newly sequenced and 230 existing HSV genome sequences, we comprehensively assessed interspecies recombination in HSV. RESULTS:Our findings show that the sizes and locations of interspecies recombination events in HSV-2 are significantly more variable than previously appreciated and that they can impact species-specific T-cell recognition of HSV. CONCLUSIONS:We describe 2 large (>5 kb) recombination events, one of which arose in its current host, demonstrating that interspecies recombination continues to occur today. These results raise concerns about the use of live-attenuated HSV-2 vaccines in high HSV-1 prevalence areas.