Tracing 2500 years of human betaherpesvirus 6A and 6B diversity through ancient DNA.
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Guellil, M., van Dorp, L., Saag, L., Beneker, O., Bonucci, B., Sasso, S., Saupe, T., Solnik, A., Kabral, H., Allmäe, R., Bates, J., Dittmar, J.M., Ge, X.J., Inskip, S., Jonuks, T., Karmanov, V.N., Khartanovich, V.I., Larmuseau, M.H.D., Aneli, S., Cessford, C., Kriiska, A., Mägi, M., Malve, M., De Winter, N., Metspalu, M., Pagani, L., Robb, J.E., Kivisild, T., Houldcroft, C.J., Scheib, C.L., Tambets, K., 2026. Tracing 2500 years of human betaherpesvirus 6A and 6B diversity through ancient DNA. Science Advances 12, eadx5460.
Abstract
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.