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Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene translation initiation

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  • Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene translation initiation

    Virology. 2017 May 26;508:170-179. doi: 10.1016/j.virol.2017.05.009. [Epub ahead of print]
    Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene translation initiation.

    Wang BX1, Brown EG2, Fish EN3.
    Author information

    Abstract

    Influenza A virus (IAV) non-structural protein 1 (NS1) suppresses host innate immune responses by inhibiting type I interferon (IFN) production. We provide evidence that residues F103 and M106 in the CPSF4-binding domain of A/HK/1/68 [H3N2] NS1 contribute to post-transcriptional inhibition of antiviral IFN-stimulated genes (ISGs), thereby suppressing an antiviral type I IFN response. Recombinant (r) IAVs encoding F103L and M106I mutations in NS1 replicate to significantly lower viral titers in human A549 lung epithelial cells and primary type II alveolar cells. In A549 cells, rIAVs encoding these mutant NS1s induce higher levels of IFN-β production and are more sensitive to the antiviral effects of IFN-β treatment. qPCR characterization of polysomal mRNA, in the presence or absence of IFN-β treatment, identified a greater proportion of heavy polysome-associated ISGs including EIF2AK2, OAS1, and MxA in A549 cells infected with rIAVs encoding these CPSF4-binding mutant NS1s, in contrast to rIAV encoding wildtype NS1.
    Copyright ? 2017 Elsevier Inc. All rights reserved.


    KEYWORDS:

    Influenza A virus; Interferon-stimulated genes; Non-structural protein 1; Polysomes; Type I interferons

    PMID: 28554059 DOI: 10.1016/j.virol.2017.05.009
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