The contagious liver disease hepatitis B is the result of a dangerous and common virus. Today, it infects approximately 350 million people worldwide and kills more than 600,000 people a year. Its origins and evolution are largely a mystery. There have been scattered clues along the way, including a 500-year-old child mummy and 82 million-year-old bird fossils, each found with traces of the virus. But two new studies bring us many steps forward to understanding how long this virus has plagued humans and how it’s changed over time.
In a paper released Thursday in eLife, Max Planck Institute scientists report that they’ve found and sequenced three strains of hepatitis B that are up to 7,000 years old. That makes them even older than the 12 ancient hepatitis B viruses described in a paper released Wednesday in Nature, authored by scientists from the Universities of Cambridge and Copenhagen. They recovered the virus from the remains of 25 people who lived from the medieval period to the Bronze Age, including one set of remains that was 4,500 years old.
“Taken together, our results demonstrate that HBV [hepatitis B virus] already existed in Europeans 7,000 years ago and that its genomic structure closely resemble that of modern hepatitis B viruses, despite the differences before,” Ben Krause-Kyora, Ph.D., the first author of the eLife study and Max Planck Institute researcher explained in a statement released Thursday. “More ancient precursors, intermediates, and modern strains of both human and non-human primate HBV strains need to be sequenced to disentangle the complex evolution of this virus.”
Krause-Kyora and his team recovered ancient DNA from the teeth of 53 skeletons excavated from Neolithic and medieval sites in Germany, the remains dating from about 5,000 B.C. to 1,200 A.D. They detected HBV in three of these samples, the locations of which are marked by captions with black borders in the map above. Reconstructing the genomes of the three viruses revealed that all of the viruses represented extinct and distinct lineages. In the Nature study, only one of the 12 viruses was considered extinct.
The scientists note that while the medieval (Petersberg, 1020-1116 Cal AD) HBV genome is the most similar to modern strains of human HBV, it is still a separate lineage to the HBV we know today. Meanwhile, the Neolithic genomes were the most similar to each other, despite their 2,000-year difference, and they appear to be more related to the strains of HBV found in chimpanzees and gorillas living today than the strains found in humans.
“Our results reveal the great potential of ancient DNA from human skeletons to allow us to study the evolution of blood-borne viruses,” Johannes Krause, Ph.D., senior author and director of the Department of Archaeogenetics at the Max Planck Institute, said. “Previously there was doubt as to whether we would ever be able to study these diseases directly in the past.”
Today, the HBV strain that infects humans is considered to be a prototype virus of the Hepadnaviridae family, and related viruses can be found in woodchucks, ground squirrels, tree squirrels, Peking ducks, and herons. Similar viruses belonging to the Hepadnavirdae family also infect bats and other non-human primates, and, according to a 2014 study in the Brazilian Journal of Infectious Diseases, “The majority of non-human primate virus isolates are phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial.”
There is a chance that human HBV originated in primates, but more research is needed. Krause and his team have already begun to examine whether fragments of the virus lay dormant in Neanderthal fossils, which could very well push back HBV’s timeline even further into the past. The scientists behind both studies say that by understanding how the virus adapted to survive over the course of history, they might be able to determine how it will change and infect modern-day and future humans.