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Effects of hemagglutinin amino acid substitutions in H9 influenza A virus escape mutants

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Abstract

We assessed the pH optimum of fusion, HA thermostability, and in vitro replication kinetics of previously obtained influenza H9 escape mutants. The N198S mutation significantly increased the optimum pH of fusion. Four HA changes, S133N, T189A, N198D, and L226Q, were associated with a significant increase in HA thermostability compared to the wild-type virus. HA amino acid changes at positions 116, 133, 135, 157, 162, and 193 significantly decreased the replicative ability of H9 escape mutants in vitro. Monitoring of pleiotropic effects of the HA mutations found in H9 escape mutants is essential for accurate prediction of all possible outcomes of immune selection of H9 influenza A viruses.

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Acknowledgments

We dedicate this report to the memory of Dr. Nikolai V. Kaverin, M.D., Ph.D., who was a Professor and a Full Member of the Russian Academy of Sciences. Dr. Nikolai V. Kaverin was one of the most prominent Russian virologists, and as a Laboratory Head at the Ivanovsky Institute of Virology in Moscow, Russia, he has significantly contributed to the scientific knowledge of influenza virus biology and to influenza prevention in Russia.

We also thank Dr. Harry Smith (FDA) for excellent editorial assistance.

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Authors and Affiliations

  1. D. I. Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, 123098, Moscow, Russia

    Irina A. Rudneva, Tatiana A. Timofeeva, Anna V. Ignatieva & Aleksandr A. Shilov

  2. FDA CDER, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Natalia A. Ilyushina

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  1. Irina A. Rudneva
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  2. Tatiana A. Timofeeva
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  3. Anna V. Ignatieva
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  4. Aleksandr A. Shilov
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  5. Natalia A. Ilyushina
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Correspondence to Natalia A. Ilyushina.

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Rudneva, I.A., Timofeeva, T.A., Ignatieva, A.V. et al. Effects of hemagglutinin amino acid substitutions in H9 influenza A virus escape mutants. Arch Virol 161, 3515–3520 (2016). https://doi.org/10.1007/s00705-016-3038-x

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  • DOI: https://doi.org/10.1007/s00705-016-3038-x

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