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Lethal H5N1 influenza viruses escape host anti-viral cytokine responses

Nature Medicine volume 8, pages 950–954 (2002)Cite this article

An Addendum to this article was published on 05 October 2012

Abstract

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 antiviral effects of interferons and tumor necrosis factor α. 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.

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Figure 1: Dose effect and roles of NS1 and HA in H5N1/97 viruses' resistance to cytokines.
Figure 2: Role of the NS gene in the resistance of H5N1 virus to cytokines in vivo.

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Acknowledgements

We thank M. Peiris, Y. Guan and K. Shortridge for providing the H5N1 influenza viruses; S. Krauss, D. Walker, J. Humberd, P. Seiler and R. Menon for technical support; L. Twit for manuscript preparation; and S. Naron for editorial assistance. This work was supported by Public Health Service grants AI-29860, AI-95357 and CA-21765, and by the American Lebanese Syrian Associated Charities (ALSAC).

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  1. Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Sang Heui Seo, Erich Hoffmann & Robert G. Webster

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Correspondence to Robert G. Webster.

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Heui Seo, S., Hoffmann, E. & Webster, R. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8, 950–954 (2002). https://doi.org/10.1038/nm757

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