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Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants

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  • Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants

    Virus Res. 2018 May 10. pii: S0168-1702(17)30958-9. doi: 10.1016/j.virusres.2018.05.002. [Epub ahead of print]
    Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants.

    Rudneva IA1, Timofeeva TA2, Mukasheva EA1, Ignatieva AV1, Shilov AA1, Burtseva EI1, Timofeev BI1, Kaverin NV1.
    Author information

    Abstract

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We investigated pH optimum of fusion, temperatures of HA heat inactivation, in vivo and in vitro replication kinetics, and connectivity with panel of sera of survivors patients in different epidemic seasons of the previously obtained influenza H1 escape mutants. Our results showed that N133D (H3 numbering) mutation significantly lowered the pH of fusion optimum. Several amino acid substitutions, including K163 N, Q192 L, D190E, G228E, and K285 M, reduced the stability of HA as determined by heat inactivation, whereas A198E substitution is associated with significant increase in HA thermostability compared to the wild-type virus. We found that amino acid change D190 N was associated with a significant decrease in viral growth in eggs and mice. Our potential antigenic variants, except readapted variant, which contained A198E mutation, did not reach fixation in infected people. Overall, a co-variation between antigenic specificity and different HA phenotypic properties was demonstrated.


    KEYWORDS:

    Escape mutants; H1 hemagglutinin; Pandemic influenza virus; Pleiotropic antibody-neutralizing mutations

    PMID: 29753891 DOI: 10.1016/j.virusres.2018.05.002
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