Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.
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.
Hatta
M
M
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
Gao
P
P
Halfmann
P
P
Kawaoka
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds / Q000821:virology; D004274:DNA, Recombinant / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000453:epidemiology* / Q000401:mortality / Q000635:transmission / Q000821:virology*; D008168:Lung / Q000821:virology; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase; D016865:Reassortant Viruses / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004274:DNA, Recombinant; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase