Ancient Herpesviruses Found in 2,000-Year-Old Remains

For the first time in scientific history, researchers have successfully reconstructed the ancient genetic codes of Human betaherpesvirus 6A and 6B (HHV-6A/B). Utilizing DNA extracted from human skeletal remains dating back over 2,000 years, a collaborative study spearheaded by the University of Vienna and the University of Tartu has confirmed that these viruses have been intertwined with human existence since at least the Iron Age.

While modern genetics previously hinted that these pathogens co-evolved with humanity during migrations out of Africa, this new research provides the first tangible, time-stamped evidence. Published in Science Advances, the study reveals a complex evolutionary history, including the discovery that the HHV-6A strain likely lost its capacity to integrate into human DNA as it adapted over centuries.

The Unique Nature of "Sixth Disease"

HHV-6B is a ubiquitous presence in modern society, infecting approximately 90% of children before they reach the age of two. It is the primary agent behind roseola infantum, widely known as "sixth disease," which is frequently responsible for sudden fevers and seizures in toddlers. Like other members of the herpesvirus family, it typically causes a mild initial infection before entering a dormant state within the host.

However, this specific group of viruses possesses a rare biological mechanism: the ability to embed its genetic material directly into human chromosomes. This process, known as chromosomal integration, allows the virus to persist in a latent state for extended periods. More significantly, this integration can be hereditary. Approximately 1% of the global population today carries a copy of this viral DNA in every cell of their body, inherited directly from a parent rather than acquired through infection. Until this breakthrough, the historical timeline of these integration events remained a hypothesis without direct genetic proof.

Screening Ancient Genomes Across Europe

To locate these elusive viral sequences, an international consortium—including experts from the University of Cambridge and University College London—conducted a massive screening of nearly 4,000 archaeological skeletal samples. This extensive search across European sites allowed the team to identify and rebuild eleven distinct ancient herpesvirus genomes.

The findings painted a detailed map of the virus's historical footprint:

• Iron Age Italy: The oldest reconstructed genome was discovered in the remains of a young girl living between 1100 and 600 BCE.
• Medieval Occurrences: Both viral strains (6A and 6B) were identified in remains from Belgium, England, and Estonia.
• Earliest Inherited Cases: Skeletons found in England provided the first direct evidence of humans carrying the chromosomally integrated form of HHV-6B.
• Community Circulation: Excavations in Sint-Truiden, Belgium, yielded the highest concentration of cases, proving that both viral species were active within a single historic community.

According to Meriam Guellil of the University of Vienna, identifying these cases is challenging because while nearly everyone contracts the virus, only the small percentage of hereditary carriers present the viral DNA in every cell, which is necessary for ancient DNA detection. The data allows scientists to trace the virus's lineage across Europe from the 8th century BCE to the modern era.

Evolutionary Divergence and Health Implications

The reconstruction of these ancient genomes allowed researchers to pinpoint the exact locations where the virus fused with human chromosomes. Comparative analysis with modern DNA revealed that many of these integration events took place thousands of years ago and have persisted through countless generations.

The study also highlighted a divergence in evolutionary strategy. While both strains are closely related, HHV-6A appears to have evolved away from integrating into the human genome, suggesting a shift in host-virus interaction over time.

Understanding this ancient relationship has immediate relevance for modern medicine. Charlotte Houldcroft from the University of Cambridge noted that inherited HHV-6B is currently associated with an increased risk of heart disease, specifically angina. The study confirms that these inherited forms are more prevalent in the UK than elsewhere in Europe, a demographic pattern that can now be linked to ancient carriers found in Britain. This research not only illuminates the deep history of infectious disease but also demonstrates how ancient childhood infections have permanently woven themselves into the human genetic fabric.