Journal
VIRUS RESEARCH
Volume 103, Issue 1-2, Pages 107-113Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2004.02.022
Keywords
H5N1; influenza; cytokines; virulence
Categories
Funding
- NCI NIH HHS [CA-21765] Funding Source: Medline
- NIAID NIH HHS [AI-29860, AI-95357] Funding Source: Medline
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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. (C) 2004 Elsevier B.V. All rights reserved.
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