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Genetic marker may identify individuals susceptible to severe West Nile virus infection

by Ross Tomlin

David J. Tweardy, M.D.

Video introduction

Researchers at Baylor College of Medicine in Houston have found a genetic marker that may identify individuals at greater risk for life-threatening infection from the West Nile virus. Results of the study are reported in the Nov. 15 print edition of Journal of Infectious Diseases.

Using technology at the Human Genome Sequencing Center at BCM, infectious disease experts compared genomic sequences of patients with severe West Nile virus infections to those who were not affected by the disease.

Discovery of a mutation

"Why do some people who get West Nile get much sicker than others who get the virus? The answer may be in the results we obtained," said David J. Tweardy, M.D., chief of the section of infectious diseases at BCM.

Following up on the discovery of a mutation in an anti-viral gene pathway in mice that causes greater West Nile susceptibility, Baylor researchers, who are members of the faculty of both the medical school and the BCM Graduate School of Biomedical Sciences, found a single nucleotide polymorphism (SNP) or a single change in this set of genes in humans who were suffering from severe symptoms of West Nile. In essence, the SNP found in patients with severe West Nile virus infection may mimic the mutation found in mice resulting in suppression of the anti-viral pathway and more severe disease.

Tweardy cited estimates from the Center for Disease Control that more than 99 percent of those who are infected with the virus, which is spread by mosquito bites, develop little to no clinical symptoms or illness. Of the remainder, most manifest flu-like symptoms such as fever and malaise. Only a small subset of those infected develops the most severe forms of the disease -- meningitis and encephalitis, the latter of which can be fatal.

Who needs to be vaccinated?

Because only a small fraction of those who contract the virus develop life-threatening symptoms, researchers hope to use this kind of information to identify those who need to be immunized against West Nile and those who do not need the vaccination.

"We are trying to understand who would be the first group to be targeted for immunization should a vaccine become available," Tweardy said. "You might be inclined to think that everyone needs to be vaccinated, but as we are becoming increasingly sophisticated about the genomics of individuals, we may only need to vaccinate those who have a predisposition to more severe disease."

An outbreak of West Nile in the United States first occurred in 1999, creating a growing problem for health professionals who still have no consistently effective treatment for the virus. Those over the age of 60 are most vulnerable to becoming seriously ill.

Other contributors to the study included BCM faculty members Drs. Richard Gibbs, Imtiaz Yakub, Ana Moran, Omar Y. Gonzalez, and John Belmont. Dr. Kristy M. Lillibridge, a member of the infectious disease center at the University of Texas Health Science Center at Houston School of Public Health, also was a key participant.

This study was funded by the Margaret M. and Albert B. Alkek Foundation.

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