It is a sensation: For the first time, researchers have reconstructed ancient genomes of the human beta-herpesviruses 6A and 6B (HHV-6A/B) from archaeological human remains that are over two millennia old.

An international research team led by the University of Vienna and the University of Tartu (Estonia) – in collaboration with the University of Cambridge and University College London – examined nearly 4,000 human skeletal samples from archaeological sites across Europe. Eleven ancient viral genomes have been identified and reconstructed – the oldest comes from a young girl from the Iron Age in Italy (1100–600 BCE). The remaining individuals covered a wide geographical and temporal range: both HHV types were found in medieval England, Belgium and Estonia, while HHV-6B also appeared in samples from Italy and early historical Russia. Several of the English individuals carried inherited forms of HHV-6B, making them the earliest known carriers of chromosomally integrated human herpes viruses. The Belgian site of Sint-Truiden provided the largest number of cases, with both virus species circulating within the same population.

“While HHV-6 infects almost 90% of the human population at some point in their lives, only about 1% carry the virus inherited from their parents in all cells of their body. These 1% of cases are the ones we are most likely to identify using ancient DNA, which makes the search for viral sequences quite difficult,” said the study’s lead researcher, Meriam Guellil from the Department of Evolutionary Anthropology at the University of Vienna. “Based on our data, the evolution of viruses can now be traced back more than 2,500 years in Europe, using genomes from the 8th to 6th centuries BCE to the present day.”

Based on the reconstructed genomes, the researchers were able to determine in which chromosome the viruses had integrated. Comparisons with modern data revealed that some integrations are ancient and have been passed down from generation to generation over thousands of years. One of the two types of virus (HHV-6A) appears to have lost its ability to integrate into human DNA over time – evidence that these viruses evolved differently during their coexistence with humans.

“If a copy of HHV-6B is present in the genome, it may be associated with angina pectoris and heart disease,” says Charlotte Houldcroft (Department of Genetics, University of Cambridge). “We know that these heritable forms of HHV-6A and B are now more common in the UK than in the rest of Europe, and this is the first evidence of old carriers from the UK.”

HHV-6B infects about 90 percent of all children by the age of two and is best known as the cause of roseola infantum — or “sixth disease” — the most common cause of febrile seizures in young children. Together with its close relative HHV-6A, it belongs to a group of widespread human herpesviruses that typically cause lifelong, latent infections after an initially mild illness in early childhood. What makes them so extraordinary is their ability to integrate with human chromosomes – a property that allows the virus to remain dormant and, in rare cases, be inherited as part of the host’s own genome. Such inherited virus copies occur in about one percent of people today. While previous studies had hypothesized that these integrations are very old, the new data from this study provide the first direct genomic evidence of this.

Original Paper:

Meriam Guellil et al. (2025). Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA. In Science Advances (2025).

Editor: X-Press Journalistenbüro GbR

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