Study confirms that herpesviruses have co‑evolved with humans for thousands of years

Ancient DNA data have helped identify that certain herpesviruses, which most people encounter during their lifetime, became part of the human genome thousands of years ago.

Ancient DNA allows us to observe the evolution of bacteria and viruses over very long time periods. For the first time, researchers have reconstructed ancient genomes of human betaherpesviruses 6A and 6B (HHV-6A/B) from archaeological human remains that are more than two millennia old. The study, led by the University of Vienna and the University of Tartu and published in Science Advances, confirms that these viruses have evolved with humans and within humans since at least the Iron Age.

According to Kristiina Tambets, Professor of Archaeogenomics at the University of Tartu and head of the research group, it is known that HHV‑6B infects approximately 90 per cent of children within their first two years of life and is the cause of infant roseola, also known as the “sixth disease.” Together with the second species, HHV‑6A, it belongs to a widespread group of human herpesviruses that typically cause a mild primary infection in early childhood and then persist in the body for life. What makes herpesviruses unique is their ability to remain latent in cells and, in rare cases, become inherited as part of the host genome.

Tambets notes that these viruses have been relatively understudied, leaving many questions about how the virus and human host have interacted while co‑evolving. “Our results map, for the first time using ancient DNA, the integration of betaherpesviruses into human chromosomes over a long period of time and suggest that one of the species (HHV‑6A) lost this ability early on,” she explained.

Extensive and time‑consuming virus detection

The international research team, led by the University of Vienna and the University of Tartu in collaboration with the University of Cambridge and University College London, thoroughly examined nearly 4,000 human skeletal samples from archaeological sites across Europe for traces of pathogens. They identified and reconstructed eleven viral genomes—the oldest of which originated from a young girl who lived in Iron Age Italy (1100–600 BCE). Later-period carriers covered a wide geographic range, as both types of herpesviruses were found in medieval individuals from Western, Southern, and Eastern Europe, including England, Belgium, Italy, and Estonia.

Several samples from England revealed inherited HHV‑6B, making them the earliest known carriers of chromosomally integrated human herpesviruses. The Sint‑Truiden site in Belgium showed the highest number of cases where both virus types circulated within the same population.

“Although herpesviruses infect nearly 90% of the global population at some point in life, only about one per cent carry the viral DNA in a form inherited from their parents and present in all cells of the body. These are precisely the cases most likely to be detected using ancient DNA, which makes finding viral sequences quite challenging,” said lead author Meriam Guellil, a researcher at the University of Vienna’s Department of Evolutionary Anthropology and former postdoctoral researcher in ancient pathogens at the University of Tartu. “Our data now allow us to trace the evolution of these viruses over more than 2,500 years across Europe, using genomic data from the 8th–6th centuries BCE up to the present day,” she added.

A virus that has evolved alongside us

The reconstructed genomes enabled researchers to determine which chromosomes the viruses had integrated into. Comparison with modern data revealed that some integrations occurred a very long time ago and have been passed down through generations for millennia. The fact that one of the two virus types (HHV-6A) appears to have lost the ability to integrate into human DNA over time suggests that the viruses have evolved differently in tandem with humans.

Professor Kristiina Tambets emphasises that this ancient‑DNA‑based study helps us understand viruses that were only discovered in the 1980s. “Thanks to this research, we now know that the virus has not only accompanied humans for thousands of years but has also co‑evolved with us at the genomic level during that time,” she said. According to the researchers, the shared history of herpesviruses and humans may even extend back to the first human migrations out of Africa.

Read the study: Meriam Guellil et al. (2025). Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA. Science Advances (2025). DOI: 10.1126/sciadv.adx5460