Researcher uses federal grant to investigate West Nile Virus

Georgia State University’s Margo Brinton, a Regents’ Professor in the Department of Biology, received a $289,000 federal stimulus grant from the National Institutes of Health to continue her research on West Nile virus, which is transmitted to humans by mosquitoes.

West Nile virus causes either a mild illness characterized by short-term flu-like symptoms or no symptoms at all in most people it infects. But for some, infection results in severe illness, with the possibility of permanent neurological effects or death, according to the Centers for Disease Control and Prevention.

Specifically, this grant will focus on studies aimed at understanding how West Nile virus manipulates and commandeers cell proteins and processes to enhance its own replication.

“By gaining a detailed understanding these complicated interactions, we’re defining new targets for the development of antiviral therapies, and we’re also learning more about cell functions,” Brinton said.

Another of the projects ongoing in Brinton’s lab is focused on understanding why a small number of people infected with West Nile virus become extremely ill, even though they have normal responses to infections with other types of viruses. This work may lead to the development of a way to identify individuals who are highly susceptible to West Nile virus. These would be good candidates for vaccination with a “killed” vaccine but not a “live” one for this virus.

The idea that genetic factors could control the severity of the disease developed by individual humans after infection with West Nile virus is based in part on work done by Brinton’s lab on mice. In mice, a single, dominant gene determines whether a mouse lives or dies after a West Nile infection. Although the general location of this gene in the mouse DNA genome had been determined, the identity of the gene was not known until 2002, when Brinton’s lab compared a region of 650,000 DNA base pairs in resistant and susceptible mice and found the single change between them that made the difference.

Brinton, who first came to Georgia State in 1989, has been working on West Nile virus since the 1960s. “In the 1960s, West Nile virus was circulating primarily in Africa and the Middle East and was thought to cause only mild disease symptoms in humans,” Brinton said. One group of physicians thought that this virus was safe enough to be used to help cancer patients by generating interferon – a cell proteins made and released in response to pathogens that can act against tumors.

However, the patients – who already had weakened immune systems due to their cancer – died. Because of these human deaths, West Nile virus received a higher safety-level classification, meaning that scientists had to take more precautions when working with it. Additionally, the strain of virus that came to the United States in 1999 is more virulent than previously known strains.

Even though Brinton’s lab primarily works with less virulent strains of the virus, she and her staff take multiple precautions and work with live virus only in secure labs that are rated at Biosafety level 3, with level 4 being the highest safety rating.

For more information about West Nile virus, visit www.cdc.gov/ncidod/dvbid/westnile/index.htm.

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