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Lethal H5N1 influenza viruses are not resistant to interferon action in human, simian, porcine or chicken cells

Nature Medicine volume 18, pages 1456–1457 (2012)Cite this article

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To the Editor:

Seo et al.1 reported that highly virulent H5N1 influenza viruses were virtually totally resistant to the action of interferon-α (IFN-α), IFN-γ or tumor necrosis factor-α (TNF-α), as tested in St. Jude porcine lung (SJPL) cells. Furthermore, they concluded that the NS1 protein of these highly pathogenic viruses conferred resistance to these cytokines by virtue of a D92E substitution. This report was unprecedented because influenza viruses have been observed to be sensitive to the action of IFN2,3,4. In spite of the selective pressure exerted by evolution5, influenza viruses have not developed resistance to the action of IFN. Indeed, most infectious particles in the highly pathogenic A/TK/ONT/7732/66 (H5N9) virus population were as sensitive to IFN action as was the highly sensitive vesicular stomatitis virus (VSV)4. Although a small fraction of the infectious influenza virus population resisted the action of high doses of IFN, this resistance was transient and without a genetic basis, that is, resistance was lost following the growth of virus from plaques that arose in the presence of IFN4.

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Figure 1: Sensitivity of A/PR8/8/34 (H1N1) and H5N1-NS reassortant viruses to the action of IFNs.
Figure 2: Sensitivity to cytokine action of several influenza viruses used in the study by Seo et al.1.

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Acknowledgements

This work was supported by a donation to the Virus and Interferon Research Laboratory (P.I.M. and M.J.S.), by the US National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Department of Health and Human Services, contract number HSN266200700005C and by the American Lebanese Syrian Associated Charities (R.G.W. and S.S.-C.).

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Author notes

  1. Kareem N Mohni

    Present address: Current address: Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.,

Authors and Affiliations

  1. Department of Molecular and Cell Biology, Virus and Interferon Research Laboratory, University of Connecticut, Storrs, Connecticut, USA

    John M Ngunjiri, Kareem N Mohni, Margaret J Sekellick & Philip I Marcus

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

    Stacey Schultz-Cherry & Robert G Webster

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  1. John M Ngunjiri
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Correspondence to Philip I Marcus.

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Ngunjiri, J., Mohni, K., Sekellick, M. et al. Lethal H5N1 influenza viruses are not resistant to interferon action in human, simian, porcine or chicken cells. Nat Med 18, 1456–1457 (2012). https://doi.org/10.1038/nm.2879

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