The NS1 gene of H5N1 influenza viruses circumvents the host anti-viral cytokine responses.
The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent, but the mechanism of their virulence in humans is largely unknown. Here we show that lethal H5N1 influenza viruses, unlike other human, avian, and swine influenza viruses, are resistant to the anti-viral effects of interferons and tumor necrosis factor alpha The nonstructural (NS) gene of H5N1 viruses is associated with this resistance. Pigs infected with recombinant human H1N1 influenza virus that carried the H5N1 NS gene experienced significantly greater and more prolonged viremia, fever, and weight loss than did pigs infected with wild-type human H1N1 influenza virus. These effects required the presence of glutamic acid at position 92 of the NS1 molecule. These findings may explain the mechanism of the high virulence of H5N1 influenza viruses in humans and provide insight into the virulence of 1918 Spanish influenza.
Seo
Sang Heui
SH
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA.
Hoffmann
Erich
E
Webster
Robert G
RG
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology; D009154:Mutation; D011995:Recombination, Genetic; D013552:Swine / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000235:genetics*
D016207:Cytokines; C085820:INS1 protein, influenza virus; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; D007372:Interferons