Studies reveal methods viruses use to sidestep immune system

DALLAS Feb. 14, 2005 A series of studies by researchers at UT Southwestern Medical Center sheds light on the mechanisms used by viruses to thwart a host's immune defenses and may aid in the development of more effective drugs to fight hepatitis C and West Nile viruses, as well as the flu and the common cold.

In a study to appear in a March issue of the Journal of Virology and currently available online, UT Southwestern researchers describe how an essential gene, called RIG-I, turns on a cascade of host immune defenses when the hepatitis C virus (HCV) replicates in cultured human cells.

Those immune defenses should fight off the virus, but in a separate study, scheduled to appear online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences, the researchers show how HCV sidesteps the immune response, allowing the virus to replicate unchecked.

Dr. Michael Gale, associate professor of microbiology at UT Southwestern and senior author of the two studies, said the tactics employed by HCV to infect a host are likely to be similar to those employed by other RNA viruses such as West Nile, influenza and the common cold.

"This work has broad implications that go beyond just the hepatitis C virus, and that's what we're most excited about," said Dr. Gale. "It's a battle between viruses and humans. Viruses have co-evolved with their hosts, so every time we have evolved a gene with a new function that allows us to fight off a virus, the virus adapts and comes up with a new function of its own to counteract our defenses."

Further defining how RNA viruses target and control host immune defenses will aid in drug development to combat disease, he said.

In the Virology paper, Dr. Gale and his research group found that a specific mutation in the gene RIG-I conferred permissiveness to HCV, allowing it to replicate "like gangbusters" in those cells with the mutation, Dr. Gale said. He and his group determined that

Contact: Amanda Siegfried
UT Southwestern Medical Center

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