Tips from the journals of the American Society for Microbiology

Genes May Determine Susceptibility to H5N1 Avian Influenza A Virus Infection

A new study found genetic variations in mice affect their susceptibility to and severity of H5N1 avian influenza A virus infection suggesting that humans who contract the virus may be genetically predisposed. The researchers from St. Jude Children's Research Hospital, VA Medical Center and MidSouth Center for Biodefense and Security, and the University of Tennessee Health Science Center, Memphis, Tennessee report their findings in the October 2009 issue of the Journal of Virology.

Over the last 10 years, highly pathogenic H5N1 avian influenza A has spread from Southeast Asia into Europe and Africa killing millions of chickens and ducks along the way. It has also infected tigers, cats, dogs and humans often resulting in death. Despite the countless cases reported in birds, the number of human cases remains few and of those few more than 90% occurred in genetically related family members indicating a possible genetic correlation.

In the study researchers conducted genome-wide linkage analysis to identify chromosomes that contribute to varying susceptibility to H5N1 in two inbred strains of mice challenged with a lethal dose of a highly pathogenic H5N1 virus. Results revealed five quantitative trait loci for influenza virus resistance located on multiple chromosomes also associated with H5N1 resistance. Additionally, a number of candidate susceptibility genes were identified, one of which affected virus titers 7 days following infection.

"An important and novel finding of this study is that H5N1-induced pathology is greatly affected by genetic polymorphisms in the genome of the infected host," say the researchers. "We have also found that, at least in mice, H5N1 pathogenesis is a complex genetic trait with multiple genes affecting disease outcome."

(A.C.M. Boon, J. deBeauchamp, A. Hollmann, J. Luke, M. Kotb, S. Rowe, D. Finkelstein, G. Neale, L. Lu, R.W. Williams, R.J. Webby. 2009. Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice. Journal of Virology, 83. 20: 10417-10426.)

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