By Julie SteenhuysenPosted 2008/08/06 at 6:18 pm EDT
CHICAGO, Aug. 6, 2008 (Reuters) — Researchers have traced all of the proteins and enzymes used by the West Nile virus to infect cells, and found 305 genes that could serve as targets for treatments.
"It comprises a dictionary of all of these genes that are critical for West Nile virus infection of a cell," said Dr. Erol Fikrig of Yale University in New Haven, Connecticut, whose study was published on Wednesday in the journal Nature.
West Nile virus infected an estimated 175,000 people in the United States last year, killing 117 and causing serious disease in 1,227 people, the U.S. Centers for Disease Control and Prevention reported last month.
There is no specific treatment for the infection caused by the mosquito-borne virus.
Fikrig's team deployed a new technology using small interfering RNAs or siRNAs to scan the human genome looking for all the genes that could be hijacked by this virus.
While DNA carries the body's genetic instruction book, RNA is the genetic material that gives cells their marching orders. Small interfering RNAs are bits of genetic material that can shut down individual genes.
Using this technology, Fikrig's team was able to systematically remove 21,121 human genes to find which ones the virus uses.
"We knocked them out individually and then we infected those cells with the West Nile virus to see if the infection was reduced or increased," Fikrig said in a telephone interview.
What they found was a population of 305 genes that, once removed, altered the course of the infection. "In most cases the infection was reduced. In a few cases, it was enhanced," Fikrig said.
"That is not unexpected. Our body is meant to fight viruses," he explained.
They also looked at clusters of these genes to see what they do in the cell. They determined that to succeed, the virus needs a wide variety of molecules and cells.
Next, they extrapolated their findings to other types of viruses in the same family as West Nile, called flaviviruses, such as the dengue virus, to see if the same cells used by West Nile are important to them, too.
They found about 30 percent of the genes were used by both types of viruses.
Using this information, Fikrig said it may be possible to develop a therapy that could interfere with genes needed for West Nile, dengue and other types of flaviviruses, such tick-borne encephalitis and yellow fever.
So far, his work has only been done on cells in the lab. Fikrig said the next step will be to test the findings in mice.
West Nile, which was introduced to the United States in 1999, infects birds and can spread to people via mosquitoes that bite both.
(Editing by Maggie Fox and Xavier Briand)
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