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Alternative interaction sites in the influenza A virus nucleoprotein mediate viral escape from the importin-α7 mediated nuclear import pathway

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  • Alternative interaction sites in the influenza A virus nucleoprotein mediate viral escape from the importin-α7 mediated nuclear import pathway

    FEBS J. 2019 May 1. doi: 10.1111/febs.14868. [Epub ahead of print]
    Alternative interaction sites in the influenza A virus nucleoprotein mediate viral escape from the importin-α7 mediated nuclear import pathway.

    Resa-Infante P1, Bonet J2, Thiele S1, Alawi M1,3, Stanelle-Bertram S1, Tuku B1, Beck S1, Oliva B2, Gabriel G1,4.
    Author information

    Abstract

    Influenza A viruses are able to adapt to restrictive conditions due to their high mutation rates. Importin-α7 is a component of the nuclear import machinery required for avian-mammalian adaptation and replicative fitness in human cells. Here, we elucidate the mechanisms by which influenza A viruses may escape replicative restriction in the absence of importin-α7. To address this question, we assessed viral evolution in mice lacking the importin-α7 gene. We show that three mutations in particular occur with high frequency in the viral NP protein (G102R, M105K and D375N) in a specific structural area upon in vivo adaptation. Moreover, our findings suggest that the adaptive NP mutations mediate viral escape from importin-α7 requirement likely due to the utilization of alternative interaction sites in NP beyond the classical nuclear localization signal. However, viral escape from importin-α7 by mutations in NP is, at least in part, associated with reduced viral replication highlighting the crucial contribution of importin-α7 to replicative fitness in human cells. This article is protected by copyright. All rights reserved.
    This article is protected by copyright. All rights reserved.


    KEYWORDS:

    Influenza virus; host-pathogen interaction; nuclear transport; protein-protein interaction; virus evolution

    PMID: 31044563 DOI: 10.1111/febs.14868
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