When the Immune System Tolls

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Researchers at Cedars-Sinai Medical Center and Yale University (studying mice) pinpoint the first line of defense the immune system uses to eliminate the virus that causes North America’s most prevalent source of epidemic viral encephalitis.

Delivered from the tip of a mosquito’s proboscis, West Nile virus binds and ekes its way into cells. Once it is inside a transformation is triggered freeing the virus to usurp host equipment. It sets up shop, replicates, slides through the cell’s processing facilities, then hitches a ride with the transportation system — out and on to the next.

The lucky manage to destroy the virus before it accomplishes its goal — or at least its potential — in taking over cell after cell to ultimately conquer the brain. Most of those exposed, an estimation that likely exceeds 750,000 in the United States, experience little malaise. The unlucky, though, (about 20 percent of those infected), the immunocompromised or elderly, might have flu-like symptoms. And some will develop the severe symptoms of encephalitis including tremors, coma and …

And there’s no treatment.

The researchers’ report, published in Immunity, shows mice deficient in specific proteins fall victim to the devastating aspects of the illness. Their immune system, while reacting, fails to properly recognize the virus, hence, within two weeks of infection (by needle, not proboscis), mice short of what are known as Toll-like receptor 7s show dismal survival rates.

Toll-like receptor molecules sense pathogens. Acting as first responders, they and go on to initiate a full blown immune reaction. Bells sound, sirens scream; here comes the cavalry to the rescue.

So, using a series of mice deficient in several immune factors, the researchers determined which pathway is critical to West Nile Virus clearance. In mice that lack Toll-like receptor 7, immune cells are sent to the infected organ, including the brain, but then fail to directly target infected cells — they can’t tell the uniforms of the enemy. This alarm system and subsequent troops (immune cells that secrete the molecule IL-23) are what the researchers believe may be modified to treat West Nile virus.

“Our results suggest that drug therapy aimed at promoting this signaling pathway may enhance the immune response and thereby promote clearance of this potentially deadly virus,” Terrence Town, co-lead author of the study, was quoted in a recent press release.

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