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Scientists show that tick-borne flaviviruses use a novel mechanism to evade host defenses

fect people following a tick bite, but there are no cases of natural disease recorded. In the 1970s Langat was briefly used as a live vaccine against more virulent tick-borne encephalitis viruses in Russia but caused encephalitis complications in about 1 of every 10,000 people.

Interferon, the body's first defense against many viruses, triggers a cascade of immune defenses. According to researchers at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, MT, NS5 blocks the body's attempt to signal for immune defenses, preventing the immune system from both stopping the spread of virus and helping the body recover from infection.

Interferon is so critical for recovery from these infections that it is being tested in clinical trials to treat infection with various flaviviruses. But the treatment appears to fail in about half of cases. Dengue virus, West Nile virus and yellow fever virus have a protein called NS4B that prevents interferon from functioning properly. It was thought that the tick-borne flaviviruses would use the same protein, so the NS5 finding was unexpected.

The RML group, directed by Marshall Bloom, M.D., chose Langat virus because it is spread by ticks--a trademark of RML expertise--and because it possesses the same survival mechanisms as the more serious tick-borne encephalitis, Omsk hemorrhagic fever (found in western Siberia) and the closely related Kyasanur forest disease (found in western India).

"These diseases are spread by the same tick that carries Lyme disease in the U.S.," says Dr. Bloom. "So, the fact that West Nile virus first appeared or emerged in the U.S. in 1999 should warn us about the potential for tick-borne flaviviruses to emerge on other continents." In preparation for such a development, Dr. Fauci notes that two other NIAID laboratories have similar flavivirus studies under way, and the three groups are building on the discoveries of each other.

Dr. Bloom says that all flaviviruses have
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Source:NIH/National Institute of Allergy and Infectious Diseases


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