Researchers Find Genes That Influence West Nile Virus

WEDNESDAY Aug. 6, 2008 -- Researchers have zeroed in on more than 300 human genes that appear to impact West Nile virus infection of human cells.

Finding ways to interfere with how these genes work may provide ways to treat or even prevent infection.

"The point of the article was to determine what human genes are critical to or influence West Nile Virus infection," said Dr. Erol Fikrig, senior author of a paper in the current issue of Nature. "This indicates possible pathways for therapy."

The findings have significance not only for West Nile virus, but also for the whole family of flaviviruses, which include dengue, yellow fever, Japanese encephalitis, tick-borne encephalitis and others.

"They're interested in identifying the genetic factors that regulate susceptibility to infection with a certain class of viruses, and among those viruses are some which are of public health importance," said Philip Alcabes, an associate professor of public health at the School of Health Sciences at Hunter College, City University of New York. "In theory, if you could identify the genetic factors that make cells susceptible to infection, you could do something about that to make people less susceptible."

But what form that intervention will take is, at this point, far from clear, Alcabes warned.

Since it first appeared in North America in 1999, West Nile virus has made its way across the continent and has infected humans in virtually every contiguous state. The virus is normally passed from an infected mosquito to a bird then, from the bird, to other mosquitoes. The mosquitoes then pass the virus on to humans.

People infected with West Nile can experience a range of symptoms, from mild, flu-like aches and pains to life-threatening encephalitis (inflammation of the brain).

But the virus has a mere 10 proteins, suggesting that it uses cellular processes in the host to enable it to infect and replicate.

Using genome-wide screening, the authors of this paper identified 305 genes or proteins in human cells that affect West Nile virus infection.

Some 30 percent to 40 percent of these genes also affect infection with dengue virus. "There are some pathways that are important for both viruses," explained Fikrig, who is a professor of medicine and microbial pathogenesis at Yale University School of Medicine and an investigator with the Howard Hughes Medical Institute. "We're testing other viruses and are hopeful that some of these pathways will be important for the common family of viruses and, if so, will provide special targets for prevention."

Fikrig and his team are now trying to replicate and confirm their findings in mice. They are also testing existing compounds to see if they inhibit these pathways.

And they're hoping others will take up some of the slack.

As Fikrig pointed out, 300 genes "is more than anyone can handle on their own. I'm hopeful this will provide a road map for other people to ask these types of questions."

Another expert pointed out that the researchers have basically started to untangle how the virus uses the host's cellular processes to replicate.

"The finding has good potential to provide us with novel targets in humans that can be exploited to intervene in a wide array of viral infections," said Young Hong, assistant professor of molecular entomology at Tulane University School of Public Health and Tropical Medicine in New Orleans.

More information

Visit the U.S. Centers for Disease Control and Prevention for more on West Nile.

Posted: August 2008


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