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.
Authors
- Lehti Saag (ORCID: https://orcid.org/0000-0002-2274-8138)
- Martin Malve
- Raili Allmäe (ORCID: https://orcid.org/0000-0001-6303-947X)
- Craig Cessford (ORCID: https://orcid.org/0000-0001-7291-7828)
- Charlotte J. Houldcroft (ORCID: https://orcid.org/0000-0002-1833-5285)
- Serena Aneli (ORCID: https://orcid.org/0000-0003-4303-2507)
- Stefania Sasso (ORCID: https://orcid.org/0009-0008-1090-5731)
- Anu Solnik (ORCID: https://orcid.org/0009-0009-5615-5726)
- Biancamaria Bonucci (ORCID: https://orcid.org/0009-0001-3292-3446)
- Tina Saupe (ORCID: https://orcid.org/0000-0003-1489-9646)
- Meriam Guellil (ORCID: https://orcid.org/0000-0002-7235-4604)
- Lucy van Dorp (ORCID: https://orcid.org/0000-0002-6211-2310)
- Jenna M. Dittmar (ORCID: https://orcid.org/0000-0003-3514-1869)
- Xiangyu Ge (ORCID: https://orcid.org/0000-0001-5048-8081)
- Owyn Beneker
- Helja Kabral (ORCID: https://orcid.org/0009-0003-6068-0650)
- Mait Metspalu
- Aivar Kriiska
- Toomas Kivisild
- Kristiina Tambets (ORCID: https://orcid.org/0000-0002-8173-6380)
- Luca Pagani
- Natasja De Winter
- Marika Mägi
- Sarah Inskip
- Maarten H. D. Larmuseau
- Valeri I. Khartanovich
- Victor N. Karmanov
- John E. Robb
- Jessica Bates
- Tõnno Jonuks
- Christiana L. Scheib
Institutions
- Uppsala University (SE)
- University of Vienna (AT)
- University of Padua (IT)
- University of Leicester (GB)
- Estonian Information Technology College (EE)
- Tallinn University (EE)
- University of Cambridge (GB)
- Estonian Literary Museum (EE)
- Open Targets (GB)
- Peter the Great's Museum of Anthropology and Ethnography (RU)
- Institute of Geology, Komi Science Centre (RU)
- Institute of Genetics (HU)
- Department of Archaeology (LK)
- Estonian Biocentre (EE)
- University College London (GB)
- University of York (GB)
- University of Turin (IT)
- University of Tartu (EE)
- Edward Via College of Osteopathic Medicine (US)
- KU Leuven (BE)
Publication Details
- Journal
- Science Advances
- Published
- 2026-01-02
- DOI
- https://doi.org/10.1126/sciadv.adx5460
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 0.00