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Complex Genetic Variations in Bird Flu in Vietnam

Recombinomics Commentary
February 9, 2005

>> The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets……..

Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference. <<

The above comments, published this month in Journal of Virology, indicate that the isolates from H5N1 Vietnam last season produced differential results in a ferret experimental model.  All of the human isolates and 2 of 9 avian isolates were extremely pathogenic in ferrets.  However, none of the isolates had human genes and the differences between the more pathogenic and less pathogenic isolates were complex, involving multiple genes and multiple genetic alterations.

The H5N1 isolates this season in Vietnam have additional genetic changes, which could alter the clinical presentation of the disease and affect case fatality ratios, which are much higher in the south.  The above comments also identify neurotropism in some of the isolates and extended this neurotropism to another mammal, ferrets.  The ferrets also had hind leg paralysis.

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