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Effects of the S42 residue of the H1N1 swine influenza virus NS1 protein on interferon responses and virus replication

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  • Effects of the S42 residue of the H1N1 swine influenza virus NS1 protein on interferon responses and virus replication

    Virol J. 2018 Mar 27;15(1):57. doi: 10.1186/s12985-018-0971-1.
    Effects of the S42 residue of the H1N1 swine influenza virus NS1 protein on interferon responses and virus replication.

    Cheng J1, Zhang C1, Tao J1, Li B1, Shi Y1, Liu H2.
    Author information

    Abstract

    BACKGROUND:

    The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response. In the avian influenza virus or human influenza virus, specific amino acids of NS1 have been shown to be important for the virus to antagonize host antiviral defenses and promote viral replication. However, little research has been reported regarding the swine influenza virus (SIV) NS1 protein.
    METHODS:

    To study the effects of the key amino acids of NS1, we rescued NS1 mutants (S42P, D92E, and S42P/D92E) of the A/swine/Shanghai/3/2014(H1N1) strain and compared their replication ability and cytokine production as well as the intracellular localization in cultured cells.
    RESULTS:

    We found that the S42P and D92E mutation displayed no changes on NS1 nuclear localization. The S42P (but not D92E) mutation suppressed protein synthesis and reduced virus growth properties, and there was an inability to antagonize host cell interferon production and IRF3 activation, which led to high levels of IFN-α and IFN-β production.
    CONCLUSION:

    We conclude that the S42 residue of the NS1 of the A/swine/Shanghai/3/2014(H1N1) strain is the key amino acid in regulating the host IFN response by blocking the activation of IRF3 and thus facilitates virus replication.


    KEYWORDS:

    Amino acids substitution; Interferon responses; NS1 protein; Swine influenza virus

    PMID: 29587786 PMCID: PMC5870223 DOI: 10.1186/s12985-018-0971-1
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