Scientists have, for the first time, rebuilt ancient genomes of Human betaherpesvirus 6A and 6B (HHV-6A/B) using DNA from archaeological human remains that are more than 2,000 years old. The research, led by teams at the University of Vienna and the University of Tartu (Estonia) and published in Science Advances, shows that these viruses have been closely linked with humans since at least the Iron Age. The findings confirm a long evolutionary relationship and reveal that one strain, HHV-6A, appears to have lost its ability to integrate into human DNA early in its history.

HHV-6B infects roughly 90 percent of children by age two and is best known for causing roseola infantum -- or "sixth disease" -- the most common cause of febrile seizures in young children. Along with its close relative HHV-6A, it belongs to a widespread group of herpesviruses that typically cause a mild early infection before remaining dormant in the body for life.

What sets these viruses apart is their unusual ability to insert their genetic material into human chromosomes. This allows the virus to stay inactive for long periods and, in rare cases, be passed down from parent to child as part of the human genome. Today, about one percent of people carry these inherited viral copies. While scientists had long suspected that these integrations occurred far in the past, direct genetic evidence had been missing until now.

Searching for Viral DNA in Ancient Human Remains

To uncover that evidence, an international team led by the University of Vienna and the University of Tartu (Estonia), working with researchers from the University of Cambridge and University College London, analyzed nearly 4,000 human skeletal samples from archaeological sites across Europe. From this large dataset, the team successfully identified and reconstructed eleven ancient herpesvirus genomes.

The oldest genome came from a young girl who lived in Iron Age Italy (1100-600 BCE). Other samples spanned a wide range of locations and time periods. Both HHV-6A and HHV-6B were detected in medieval remains from England, Belgium, and Estonia, while HHV-6B was also found in ancient samples from Italy and early historic Russia. Several individuals from England carried inherited forms of HHV-6B, making them the earliest known cases of chromosomally integrated human herpesviruses. The Belgian site of Sint-Truiden stood out, yielding the highest number of cases and evidence that both viral species circulated within the same community.

"While HHV-6 infects almost 90% of the human population at some point in their life, only around 1% carry the virus, which was inherited from your parents, in all cells of their body. These 1% of cases are what we are most likely to identify using ancient DNA, making the search for viral sequences quite difficult," said the lead researcher of the study, Meriam Guellil, University of Vienna, Department of Evolutionary Anthropology. "Based on our data, the viruses' evolution can now be traced over more than 2,500 years across Europe, using genomes from the 8th-6th century BCE until today."