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Clues to HBV Therapy from Ancient History
Oldest viral genomes show infection stretching back 4500 years
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by Pippa Wysong
Contributing Writer, MedPage Today
This Reading Room is a collaboration between MedPage Today® and: Medpage Today
Expert Critique
FROM THE AGA Reading Room
Melody H. Hermel, MD PGY-1 Resident LAC+USC Internal Medicine Los Angeles, CA
A key to understanding hepatitis B virus (HBV) may be in the study of the ancient origins of the virus and how it has evolved over time. Recently, researchers have harnessed advances in sequencing of ancient DNA to detect HBV infection in individuals who lived over 4,000 years ago. Following the ancient roots of HBV may increase our understanding of the virus and the breadth of mutations HBV has undergone over time, which may help with the development of future vaccines or therapies. Additionally, from an anthropologic perspective, we will gain insights into human migration and interaction by following the patterns of HBV spread and mutation over time, which could unlock clues to human history.
Hepatitis B virus (HBV) has been in the human population for a while, and researchers now have evidence showing it's been infecting humans for least 4,500 years.
This ups the ante, since previous genetic detective work on historic samples had gone back only 400 years. The new research represents the oldest viral genomes recovered from human or vertebrate samples, the authors said.
The findings come from two studies published in Nature by Eske Willerslev, DSc., and colleagues. In one paper, DNA was sequenced from 304 individuals who lived between about 200 and 7,000 years ago in central and western Eurasia. Evidence of HBV infections was found in 25 people, ranging throughout a period of close to 4,000 years.
In the second study, genome sequences were done of 137 ancient humans from the Eurasian steppes -- a region about 8,000 km long extending from Hungary to northeastern China. The researchers used samples covering a period of about 4,000 years and recovered 12 full or partial HBV genomes.
The team also used genomic data from 502 individuals from present-day self-reported ancestries across Central Asia, Altai, Siberia, and the Caucasus for comparisons. The findings shed light on the population history of the region, including clues about how the virus spread across these regions as people moved.
"Recent advances in the sequencing of ancient DNA have yielded important insights into human evolution, past population dynamics, and diseases," the authors wrote. The actual root of the HBV tree is projected to be between 8.6 thousand and 20.9 thousand years ago, and genetic detective work on ancient samples is slowly showing the path of the viruses' origin and evolution.
The first author of the DNA-sequencing study, Barbara Muhlemann, a zoologist from the University of Cambridge in the U.K., told the Reading Room that the estimate of the age of the HBV tree comes from a molecular dating analysis that calculates when the modern and ancient sequences last shared a common ancestor.
According to one of the papers, the genome properties follow those of modern HBV, although the researchers also uncovered some HBV genotypes that are now extinct. "These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone," the authors wrote.
Expanding on this, Muhlemann said that the fact that they found numerous genetic variations not seen in present-day viruses, including in Bronze Age individuals, "is important because it gives us a range of genetic variants that can be tested, whereas before we couldn't know what kinds of mutations would produce viable viruses."
In other words, she said, variations from the past provide "a library of possible future variants which can help us prepare, can help with surveillance, and could be used to make the vaccine more broadly protective. Without this information we're completely in the dark with respect to the possible future evolution of the virus."
Looking at the past, she added, can also provide clues as to how likely it might be for the modern virus to change in dramatic ways that may need a quick response.
last updated 09.20.2018
Primary Source
Nature
Source Reference: Mühlemann B, et al "Ancient hepatitis B viruses from the Bronze Age to the Medieval period" Nature 2018; DOI: 10.1038/s41586-018-0097-z. |
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发表于 2018-9-21 20:09