Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA

Kristiina Tambets; Mait Metspalu; Aivar Kriiska; Xiangyu Jack Ge; Serena Aneli; Martin Malve; Helja Kabral; Lehti Saag; Toomas Kivisild; John Robb; Anu Solnik; Lucy van Dorp; Christiana Lyn Scheib; Luca Pagani; Raili Allmäe; Valeri I. Khartanovich; Meriam Guellil; Sarah Alice Inskip; Stefania Sasso; Natasja De Winter; Owyn Beneker; Biancamaria Bonucci; Tina Saupe; Marika Mägi; Craig Cessford; Maarten H.D. Larmuseau; Victor N. Karmanov; Tõnno Jonuks; Jessica Bates; Jenna M. Dittmar; Charlotte J Houldcroft

doi:10.1126/sciadv.adx5460

Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA

Kristiina Tambets
, Mait Metspalu
, Aivar Kriiska
, Xiangyu Jack Ge
, Serena Aneli
, Martin Malve
, Helja Kabral
, Lehti Saag
, Toomas Kivisild
, John Robb
, Anu Solnik
, Lucy van Dorp
, Christiana Lyn Scheib
, Luca Pagani
, Raili Allmäe
, Valeri I. Khartanovich
, Meriam Guellil
, Sarah Alice Inskip
, Stefania Sasso
, Natasja De Winter

Owyn Beneker, Biancamaria Bonucci, Tina Saupe, Marika Mägi, Craig Cessford, Maarten H.D. Larmuseau, Victor N. Karmanov, Tõnno Jonuks, Jessica Bates, Jenna M. Dittmar, Charlotte J Houldcroft

School of the Human Environment

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	eadx5460
Journal	Science Advances
Volume	12
Issue number	1
DOIs	https://doi.org/10.1126/sciadv.adx5460
Publication status	Published - 2 Jan 2026

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Tambets, K., Metspalu, M., Kriiska, A., Ge, X. J., Aneli, S., Malve, M., Kabral, H., Saag, L., Kivisild, T., Robb, J., Solnik, A., van Dorp, L., Scheib, C. L., Pagani, L., Allmäe, R., Khartanovich, V. I., Guellil, M., Inskip, S. A., Sasso, S., ... Houldcroft, C. J. (2026). Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA. Science Advances, 12(1), Article eadx5460. https://doi.org/10.1126/sciadv.adx5460

@article{5ce9aadc042b4c67b3c71f5049b018dd,

title = "Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA",

abstract = "Human betaherpesviruses 6A and 6B (HHV-6A/6B) are DNA viruses, which integrate into the human genome, and are best known to cause {\textquotedblleft}sixth disease.{\textquotedblright} 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.",

author = "Kristiina Tambets and Mait Metspalu and Aivar Kriiska and Ge, \{Xiangyu Jack\} and Serena Aneli and Martin Malve and Helja Kabral and Lehti Saag and Toomas Kivisild and John Robb and Anu Solnik and \{van Dorp\}, Lucy and Scheib, \{Christiana Lyn\} and Luca Pagani and Raili Allm{\"a}e and Khartanovich, \{Valeri I.\} and Meriam Guellil and Inskip, \{Sarah Alice\} and Stefania Sasso and Winter, \{Natasja De\} and Owyn Beneker and Biancamaria Bonucci and Tina Saupe and Marika M{\"a}gi and Craig Cessford and Larmuseau, \{Maarten H.D.\} and Karmanov, \{Victor N.\} and T{\~o}nno Jonuks and Jessica Bates and Dittmar, \{Jenna M.\} and Houldcroft, \{Charlotte J\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors",

year = "2026",

month = jan,

day = "2",

doi = "10.1126/sciadv.adx5460",

language = "English",

volume = "12",

journal = "Science Advances",

issn = "2375-2548",

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Tambets, K, Metspalu, M, Kriiska, A, Ge, XJ, Aneli, S, Malve, M, Kabral, H, Saag, L, Kivisild, T, Robb, J, Solnik, A, van Dorp, L, Scheib, CL, Pagani, L, Allmäe, R, Khartanovich, VI, Guellil, M, Inskip, SA, Sasso, S, Winter, ND, Beneker, O, Bonucci, B, Saupe, T, Mägi, M, Cessford, C, Larmuseau, MHD, Karmanov, VN, Jonuks, T, Bates, J, Dittmar, JM & Houldcroft, CJ 2026, 'Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA', Science Advances, vol. 12, no. 1, eadx5460. https://doi.org/10.1126/sciadv.adx5460

TY - JOUR

T1 - Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA

AU - Tambets, Kristiina

AU - Metspalu, Mait

AU - Kriiska, Aivar

AU - Ge, Xiangyu Jack

AU - Aneli, Serena

AU - Malve, Martin

AU - Kabral, Helja

AU - Saag, Lehti

AU - Kivisild, Toomas

AU - Robb, John

AU - Solnik, Anu

AU - van Dorp, Lucy

AU - Scheib, Christiana Lyn

AU - Pagani, Luca

AU - Allmäe, Raili

AU - Khartanovich, Valeri I.

AU - Guellil, Meriam

AU - Inskip, Sarah Alice

AU - Sasso, Stefania

AU - Winter, Natasja De

AU - Beneker, Owyn

AU - Bonucci, Biancamaria

AU - Saupe, Tina

AU - Mägi, Marika

AU - Cessford, Craig

AU - Larmuseau, Maarten H.D.

AU - Karmanov, Victor N.

AU - Jonuks, Tõnno

AU - Bates, Jessica

AU - Dittmar, Jenna M.

AU - Houldcroft, Charlotte J

PY - 2026/1/2

Y1 - 2026/1/2

N2 - 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.

AB - 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.

UR - https://www.science.org/doi/10.1126/sciadv.adx5460

U2 - 10.1126/sciadv.adx5460

DO - 10.1126/sciadv.adx5460

M3 - Article

SN - 2375-2548

VL - 12

JO - Science Advances

JF - Science Advances

IS - 1

M1 - eadx5460

ER -

Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA

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