Tracing 2500 years of human betaherpesvirus 6A and 6B diversity through ancient DNA

Human betaherpesviruses 6A and 6B (HHV-6A/6B) are DNA viruses, which integrate into the human genome, and are best known to cause "sixth disease." Despite their recent discovery (1980s), they were speculated to have a much longer history within the human population than modern data suggest. We present the first 11 ancient genomes of HHV-6A and HHV-6B, dating as far back as the 8th to 6th century BCE. We demonstrate that large fractions of current HHV-6 diversity were already established by the 14th century CE. Our data corroborate that HHV-6A/6B integrations stem from ancient founder events. In addition, we show that all known inherited chromosomally integrated HHV-6A clades were already represented in historical populations, confirming that HHV-6A no longer integrates into the germ line within populations of European ancestry and likely endogenized in early human history.