Unearthing the complexities of HBV in skeletons from the Bronze Age, Medieval era

Researchers have unearthed the oldest evidence of hepatitis B virus (HBV) in ancient skeletons and have found proof that viruses can become extinct.

Humans may have been afflicted by HBV as early as the Bronze Age—from approximately 3,300 BC to 1,200 BC in the Middle East and parts of Asia, according to researchers from the Center for Pathogen Evolution, Department of Zoology, University of Cambridge in the United Kingdom, and the Centre for GeoGenetics, University of Copenhagen in Denmark.

Their research comprises the oldest and largest dataset of ancient human viruses. The oldest human viruses previously discovered by scientists were only 450 years old; this new dataset goes back 4,500 years. The researchers published their findings inNature and have brought new information to light on the origins and evolution of HBV. An understanding of the genetic makeup of this strain may help improve current HBV vaccines.

“People have tried to unravel the history of HBV for decades—this study transforms our understanding of the virus and proves it affected people as far back as the Bronze Age. We have also shown that it is possible to recover viral sequences from samples of this age, which will have much wider scientific implications,” said joint first author Barbara Mühlemann, graduate student, University of Cambridge.

Dr. Mühlemann and fellow researchers sampled skeletons, dating from the Bronze Age to the Medieval period, from across Europe and Asia. From these genetic samples, they identified 25 HBV-positive skeletons, and material from 12 of these—the oldest being 4,500 years old—provided enough of the HBV genome to allow for detailed analyses.

Properties of the HBV genome, they found, follow those of modern HBV. Importantly, they also discovered a human genotype of HBV that is now extinct, evidence of the creation of HBV genotype A through recombination, and a long-term association of modern HBV genotypes with humans.

In addition, the researchers found that the geographic locations of these genotypes did not match those of present-day HBV. For example, genotypes typical of current day Africa and Asia along with a subgenotype from India, were present in early Eurasia. These geographical patterns of modern and ancient HBV genotypes are consistent with the human migrations that occurred during both the Bronze and Iron Ages.

Shining a light on HBV

The origins and evolution of HBV are largely unknown, due to a lack of historical evidence.

“Scientists mostly study modern virus strains and we have mainly been in the dark regarding ancient sequences—until now. It was like trying to study evolution without fossils. If we only studied the animals living today it would give us a very inaccurate picture of their evolution—it is the same with viruses,” said Dr. Terry Jones, joint first author, Department of Zoology, University of Cambridge.

This is a huge scientific advancement, as previous estimates had placed the virus as being active from 400 to 34,000 years. Professor Eske Willersley, St. John’s College, University of Cambridge, and the University of Copenhagen, led the research.

“Th[ese] data give us an idea of how this virus behaves, and it provides us with a better idea of what is biologically possible in the future. Analysis of other ancient DNA samples may reveal further discoveries, and this pioneering study could have huge implications for how the virus affects humans today,” he said.

“This study is just the start. We’re talking about one virus here, but there are a lot of other viruses we could look for,” concluded Professor Willersley.