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United States Department of Agriculture

Agricultural Research Service

Title: Molecular Correlates of Influenza a H5n1 Virus Pathogenesis in Mice

Authors
item Katz,, Jacqueline - CDC -ATLANTA, GA
item Lu,, Xiuhua - CDC - ATLANTA, GA
item Tumpey, Terrence
item Smith,, Catherine - CDC - ATLANTA, GA
item Shaw,, Michael - CDC - ATLANTA, GA
item Subbarao,, Kanta - CDC - ATLANTA, GA

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 23, 2000
Publication Date: November 1, 2000

Interpretive Summary: In 1997 in Hong Kong, 18 human cases of respiratory illness were caused by an avian influenza A H5N1 virus. Although avian influenza viruses had not previously been known to cause respiratory illness in humans, the H5N1 viruses caused severe illness and death, primarily in individuals aged greater than 12 years. The introduction of H5N1 viruses into humans raised dconcerns about the potential of these viruses to cause a pandemic. We hav used the BALB/c mouse to better understand the pathogenesis of the H5N1 viruses in a mammalian model. In addition, genetic differences were determined by nucleotide sequencing. It was found that there were two general types of H5N1 viruses, high and low lethality for mice. The sequence analysis determined slight differences between viruses of high and low lethality for mice. The molecular determinants between viruses of different pathogenicity provide a framework for the future identification of influenza viruses with the potential to cause severe disease.

Technical Abstract: Highly pathogenic avian influenza A H5N1 viruses caused an outbreak of human respiratory illness in Hong Kong. Of 15 human H5N1 isolates characterized, nine displayed a high pathogenecity, five a low pathogenecity, and one an intermediate pathogenicity phenotype in the BALB/c mouse model. Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. Alone or in combination, these specific residues are the likely determinants of virulence of human H5N1 influenza viruses in this model.

Last Modified: 10/20/2014
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