Ancient skeletons reveal viruses embedded in human DNA

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."

Viral Integrations That Lasted for Millennia

By reconstructing these ancient genomes, researchers were able to pinpoint where the viruses had integrated into human chromosomes. When compared with modern genetic data, the results showed that some viral integrations occurred thousands of years ago and were passed down through many generations.

The analysis also revealed that HHV-6A and HHV-6B followed different evolutionary paths. One of the two viruses, HHV-6A, appears to have lost its ability to integrate into human DNA over time, suggesting that its interaction with human hosts changed as both evolved together.

Modern Health Links and Ancient Origins

"Carrying a copy of HHV6B in your genome has been linked to angina-heart-disease," says Charlotte Houldcroft (Department of Genetics, University of Cambridge). "We know that these inherited forms of HHV6A and B are more common in the UK today compared to the rest of Europe, and this is the first evidence of ancient carriers from Britain."

A New Window Into Virus and Human Coevolution

The discovery of ancient HHV-6 genomes provides the first time-stamped genetic proof of long-term virus-human coevolution at the DNA level. It also highlights how ancient DNA can illuminate the deep history of infectious diseases, showing how short-lived childhood infections can eventually become part of the human genome.

Although HHV-6A and HHV-6B were only identified in the 1980s, this research traces their presence back to the Iron Age. "Modern genetic data suggested that HHV-6 may have been evolving with humans since our migration out of Africa," says Guellil. "These ancient genomes now provide first concrete proof of their presence in the deep human past."