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Genetic fossils betray hepatitis B's ancient roots

Modern bird genomes reveal evidence that virus is at least 82 million years old

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A virus that causes liver diseases in people may have infected birds that shared the planet with dinosaurs.

More than 82 million years ago, a hepatitis B virus infected an ancient bird and got stuck in its genome, a molecular version of a tar pit, researchers report April 30 in Nature Communications. Using fragments of DNA found in modern-day zebra finches, evolutionary biologist Alexander Suh and colleagues at the University of Münster in Germany pieced together a complete genome of the ancient virus. Their analysis suggests that hepatitis B is some 63 million years older than previously thought and that it probably originated in birds and jumped into mammals later.

The discovery is the latest find for paleovirologists, scientists who dig into the DNA of living organisms to find viruses that, at some point in the past, inserted themselves into their host’s genome and stayed there, essentially providing a genetic fossil record. Hepatitis B doesn’t normally insert itself into the genome of an infected person or animal. But in 2010, Cedric Feschotte of the University of Utah found traces of hepatitis B lurking in the zebra finch genome. Using viral DNA fragments, Feschotte calculated the virus’s age as about 20 million years old.

For the new study, Suh and his colleagues cataloged remnants of the virus in various bird species . By looking at how long ago those birds’ common ancestors lived, Suh’s team calculated the age of the virus. It turned out that the common ancestor of all birds carrying remnants of the virus lived about 82 million years ago.

Given the breadth of data that Suh’s team worked with, the extreme age of the virus didn’t surprise Feschotte. “But,” he adds, “I think it’s pretty cool.”

The reconstructed Mesozoic-era virus is remarkably similar to the hepatitis B virus that infects people today, the team found. “We’ve had 82 million years of evolution, but they have the same proteins,” says Suh, who now works at Uppsala University in Sweden.

One exception is a notorious protein called X protein. The protein has been implicated in causing liver cancer and is necessary for the virus to replicate in humans. Since X protein is missing from the hepatitis B viruses that infect modern-day birds, many scientists thought that bird viruses had lost the protein during evolution. But the ancient virus doesn’t contain X protein either, which means that the bird version probably never had it, and X marked mammalian hepatitis B viruses only recently.

Synthesizing a complete ancient hepatitis B virus, rather than simply analyzing its sequence, may help scientists understand how the prototype worked and may give insights into how the virus and its hosts have evolved together, Feschotte says. He acknowledges that many people think that reviving viruses would be a bad idea, but says that researchers could learn nearly as much by resuscitating individual proteins.

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