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By studying ancient viral DNA, researchers discovered hepatitis B has been present in Europe for at least 7,000 years.
There are many different types of viruses in the world, and they all share the ability to infect specific hosts (Cohen 2016). Some viruses are more virulent than others and some can only infect specific plants or animals (Geoghehan 2018). Recent technological developments have enabled scientists to track and record viral mutations in specific viruses in order to determine their evolution (Korber et al. 2020). In 2018, researchers developed a digital platform called NextStrain that stores viral DNA collected by scientists and maps how viruses have evolved over time (Bedford et al.). Since most viral data is from the last few years, it is difficult to reconstruct evolutionary history before the 20th century. To account for this, researchers are expanding their viral DNA library by studying extinct strains of viruses to determine how they evolved into modern strains.
One of the best ways to track the evolutionary history of viruses is by using paleogenomics. Paleogenomics is the study of ancient DNA that can be extracted from bones or fossils (Tsosie et al. 2020). Even though the viruses in remains are inactive, viral genetic material remains present in the host (Spinney 2020). By identifying viral DNA in remains and comparing the DNA to modern viruses, scientists are able to determine virus type.
Hepatitis B virus is one of the most widespread human pathogens, but not much is known about its evolution (Revill et al. 2019). In their paper, Neolithic and medieval virus genomes reveal complex evolution of hepatitis B, Krause-Kyora et al. sought to track the evolutionary history of the hepatitis B virus(2018).
Researchers first extracted hepatitis B DNA from individuals who were infected with the virus. They found three ideal human tooth samples from Europe and two flesh samples from a Korean and an Italian mummy. The teeth from 5056-4959 BC were excavated from the Neolithic site of Karsdorf, Germany, and the teeth from 3335-3107 BC were excavated from the Neolithic site of Sorsum, Germany. The more modern teeth samples were dated to AD 1020-1116 and found at the Medieval site of Petersberg, Germany. (The researchers mainly focused their analysis on the tooth samples rather than the flesh samples, as the teeth had much higher concentrations of viral DNA.)
Archeological evidence determined when the samples were alive, but Krause-Kyora et al. also wanted to use biological comparisons to confirm their findings. To do this, researchers compared the collected tooth DNA to DNA from other individuals previously found in similar locations and time periods. In all cases, the biological evidence aligned with archeological evidence, confirming when the samples were alive.
Knowing their dates were accurate, researchers then traced evolutionary paths from the oldest viruses to the newest. The Neolithic viruses (Karsdorf and Sorsum) were not similar to any other modern human hepatitis B viral strains; instead, the ancient viruses were most similar to a strand of hepatitis B that infects African, non-human primates (apes).
Even though the Neolithic samples were found almost 2,000 years apart from each other, they showed more viral similarity to each other than to any modern hepatitis B virus. The researchers concluded this might be because the older virus from Karsdorf was an ancestor for the younger Sorsum virus. Also, since the Neolithic hepatitis B viral strains are most closely related to the non-human primate viral strains, the researchers posit there must have been a point in the virus’s evolutionary history where the virus evolved to jump from infecting humans to infecting apes.
Typically, it is difficult to tell if an ancient virus was particularly virulent or if the virus was the cause of death. Interestingly, the researchers were able to make some predictions about the host-virus relationship based on the high concentration of hepatitis B DNA in the tooth samples. High viral DNA concentration in teeth was a strong indicator the individual died while infected. (The researchers make a point to note that just because a person was infected with the virus does not necessarily mean the virus was the cause of death.)
While this paper proves the hepatitis B virus existed in Europeans at least 7,000 years ago, it leaves many unanswered questions. There are still evolutionary mutations and shifts unaccounted for, specifically the mutation, or mutations, that enabled the Neolithic hepatitis B to jump from infecting humans to infecting apes. While it would be interesting to study the mutations involved in this cross-species leap, it also leads one to wonder which ancient hepatitis B strain actually led to the modern strain that infects humans. Discovering which mutations enabled a virus to infect humans could be critical in understanding how the hepatitis B virus attacks the body. Currently, there is a large evolutionary gap from 3107 BCE – AD 1020 where we have minimal hepatitis B data, so continued research in this timeframe could help reveal the missing viral data.
Despite the limited sample size, this study revealed an unexpected complexity in the evolution of the hepatitis B virus and showed the value of using paleogenomics to track the evolution of hepatitis B and other blood borne viruses. This type of study opens the door for researchers to expand the current scope of viral studies and to build a solid data bank to help aid critical viral discoveries.
Walker A. Willis is currently enrolled in Davidson College. Contact him at wawillis@davidson.edu.
References
Bedford, T., Neher, R., Hadfield, J., Hodcroft, E., Sibley, T., Huddleston, J., Aksamentov, I., Lee, J., Fay, K., Zuber, M., Harkins, E., Ilcisin, M., Wagner, C., Moncla, L., Black, A., Bell, S., Parades, M., Megill, C., Potter, B., Sagulenko, P., and Callender, C. “Nextstrain: real-time tracking of pathogen evolution.” Bioinformatics. 2018. https://academic.oup.com/bioinformatics/article/34/23/4121/5001388.
Cohen, Fredric S. “How Viruses Invade Cells.” Biophysical journal. 110(5), 1028-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788752/.
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Revill, P.A., Chisari, F.V., Block, J.M., Dandri, M., Gehring, A.J., Guo, H., Hu, J., Kramvis, A., Lampertico, P., Janssen, H., Levrero, M., Li, W., Liang, T.J., Lim, S.G., Lu, F., Penicaud, M.C., Tavis, J.E., Thimme, R., Members of the ICE-HBV Working Groups, ICE-HBV Stakeholders Group Chairs, and Zoulim, F. “A global scientific strategy to cure hepatitis B.” The Lancet Gastroenterology & Hepatology. 10 April 2019. 4(7), 545–558. https://doi.org/10.1016/S2468-1253(19)30119-0.
Spinney L. “Smallpox and other viruses plagued humans much earlier than suspected.” Nature. 23 August 2020. 584, 30-32. https://doi.org/10.1038/d41586-020-02083-0.
Tsosie K.S., Begay R.L., Fox K., and Garrison N.A. “Generations of genomes: advances in paleogenomics technology and engagement for Indigenous people of the Americas.” Current Opinion in Genetics and Development. 2020 June. 62, 91-96. https://pubmed.ncbi.nlm.nih.gov/32721847/.
