在白亚口鱼内发现嗜肝DNA病毒

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Scientists might have just discovered the true origin of Hepatitis B — in a fish

By Darryl Fears September 28


The big news two years ago was that the genes of the hepatitis B virus were discovered in the fossils of ancient birds. These birds — forebears of modern finches and robins, crows and a host of songbirds —lived around 82 million years ago, when dinosaurs walked the Earth.

So when a team of researchers recently stumbled upon a hepatitis B-like virus in a fish, it was a surprise. They double-checked the gene sequencing in  white sucker fish from the Great Lakes region. A match in an online database of gene sequences left little doubt. They had discovered hepatitis in a creature that predates birds.

Now the mystery surrounding the age of one of the most notorious viruses on the planet has deepened. What is the origin of a virus that kills more than half a million humans each year? What organism carried it first? How was it transmitted to birds? And when was it first transmitted to mammals and primates such as humans? Science isn't close to an answer on any of those questions.


The new research isn't much help. It's a scientific first, a beginning. West Virginia University doctoral student Cassidy Hahn and her team of fish biologists were studying the genes of white suckers rarely used for genetic work, so they were forced to double-check everything they found. "We were looking for a different virus," Hahn said. "We're scientists. We're skeptical. So we did some sequencing, checked it and said, 'We have something.' "

Except her voice at the time of the discovery wasn't as flat. What they uncovered seemed like a pretty big deal, since the hepatitis B virus, part of the big family of hepatitis that causes many kinds of illnesses, including cancer, had been found only in birds and mammals previously. The find had great potential for more research to track how the virus evolved, how immune systems developed to attack it, to possibly design more effective treatments.

“This new virus is similar, but also very different from hepatitis B-like viruses found in mammals and birds, and may be a new genus,” Hahn said. How the hepatitis B-like virus is transmitted between fish is not yet understood, she said, and it is unlikely to be communicable to humans.

Hepatitis-B virus infections "manifest in various ways," said a U.S. Geological Survey statement that announced the study. They attack the livers of mammals and multiply in their cells. Acute chronic liver diseases such as fibrosis, cirrhosis, bile duct cancer and hepatocellular carcinoma are associated with the virus. About 350 million people are chronically infected with hepatitis B viruses.

"For decades, virologists have been looking for the origin of where this virus came from. If you know where it occurred, you can potentially see how it changed over time … they can work on those predictive models," said Luke R. Iwanowicz, a research biologist for the USGS in West Virginia who, along with Hahn, was an author on the research paper. It was published last week in the Journal of Virology.

Other authors include Vicki S. Blazer, Robert S. Cornman, Carla M. Conway and James R. Winton, all USGS researchers and biologists.



"After we did all the putting sequencing together ... and searched an online database ... all the parts of the virus were there," Iwanowicz said. "I’ve never had that experience before. It was pretty exciting to actually see that happen."

Iwanowicz said an excited Indiana University professor who hoped to start investigating the finding contacted him even before the paper was published. "I really found this work very interesting," said Haitao Guo, an associate professor of microbiology at the university. "I read it one week early on a Saturday night. I e-mailed Luke immediately and said, 'Come on, let’s do something.' "

Guo has studied hepatitis for more than a decade and still has a host of questions about how it came to be. He wants to track it using plasma and liver samples, and possibly create a clone, to determine how it replicates. "If it replicates better, it may replace [the hepatitis-B virus] to study some aspects of the hepadnavirus molecular biology.”

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J Virol. 2015 Sep 16. pii: JVI.01278-15. [Epub ahead of print]
Characterization of a Novel Hepadnavirus in the White Sucker (Catostomus commersonii) from the Great Lakes Region of the USA.
Hahn CM1, Iwanowicz LR2, Cornman RS3, Conway CM4, Winton JR4, Blazer VS3.
Author information
Abstract
The white sucker Catostomus commersonii is a freshwater teleost often utilized as a resident sentinel. Here, we sequenced the full genome of a hepatitis B-like virus that infects white suckers from the Great Lakes Region of the USA. Dideoxysequencing confirmed the white sucker hepatitis B virus (WSHBV) has a circular genome (3542 bp) with the prototypical codon organization of hepadnaviruses. Electron microscopy demonstrated that complete virions of approximately 40 nm were present in the plasma of infected fish. Compared to avi- and orthohepadnaviruses, sequence conservation of the core, polymerase and surface proteins was low and ranged from 16-27% at the amino acid level. An X protein homologue common to the orthohepadnaviruses was not present. The WSHBV genome included an atypical, presumptively non-coding region absent in previously described hepadnaviruses. Phylogenetic analyses confirmed WSHBV as distinct from previously documented hepadnaviruses. The level of divergence in protein sequences between WSHBV other hepadnaviruses, and the identification of an HBV-like sequence in an African cichlid provide evidence that a novel genus of the family Hepadnaviridae may need to be established that includes these hepatitis B-like viruses in fishes. Viral transcription was observed in 9.5% (16 of 169) of white suckers evaluated. The prevalence of hepatic tumors in these fish was 4.9%, of which only 2.4% were positive for both virus and hepatic tumors. These results are not sufficient to draw inferences regarding the association of WSHBV and carcinogenesis in white sucker.

IMPORTANCE:
We report the first full length genome of a hepadnavirus from fishes. Phylogenetic analysis of this genome indicates divergence from those of previously described hepadnaviruses from mammalian and avian hosts and supports the creation of a novel genus. The discovery of this novel virus may better our understanding of the evolutionary history of hepatitis B-like viruses of other hosts. In fishes, knowledge of this virus may provide insight regarding possible risk factors associated with hepatic neoplasia in the white sucker. This may also offer another model system for mechanistic research.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.


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http://jvi.asm.org/content/early/2015/09/10/JVI.01278-15.abstract

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