# Tracing 2500 years of human betaherpesvirus 6A and 6B diversity through ancient DNA

## TL;DR

This study uses ancient DNA to trace the 2500-year history of HHV-6A and HHV-6B, revealing their long-standing presence in human populations.

## Contribution

The first ancient HHV-6A and HHV-6B genomes are presented, showing their phylogenetic continuity and endogenization history.

## Key findings

- HHV-6A and HHV-6B were present in human populations as early as the 8th to 6th century BCE.
- Most current HHV-6 diversity was already established by the 14th century CE.
- All inherited HHV-6A clades were present in historical populations, indicating it no longer integrates into the human germ line in European populations.

## Abstract

Human betaherpesviruses 6A and 6B (HHV-6A/6B) are DNA viruses, which integrate into the human genome, and are best known to cause “sixth disease.” Despite their recent discovery (1980s), they were speculated to have a much longer history within the human population than modern data suggest. We present the first 11 ancient genomes of HHV-6A and HHV-6B, dating as far back as the 8th to 6th century BCE. We demonstrate that large fractions of current HHV-6 diversity were already established by the 14th century CE. Our data corroborate that HHV-6A/6B integrations stem from ancient founder events. In addition, we show that all known inherited chromosomally integrated HHV-6A clades were already represented in historical populations, confirming that HHV-6A no longer integrates into the germ line within populations of European ancestry and likely endogenized in early human history.

First ancient HHV-6 genomes reveal 2500 years of phylogenetic continuity and provide insights into the endogenization of HHV-6A.