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Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.

Science (New York, N.Y.)

Animals, Birds, virology, DNA, Recombinant, genetics, Hemagglutinin Glycoproteins, Influenza Virus, chemistry, metabolism, Hong Kong, epidemiology, Humans, Influenza A Virus, H5N1 Subtype, Influenza A virus, pathogenicity, physiology, Influenza, Human, mortality, transmission, Lung, Mice, Mutation, Missense, RNA Replicase, Reassortant Viruses, Viral Proteins, Amino Acid Sequence

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      In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.

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