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Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference

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  • Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference

    Virology. 2016 Jul 27;497:171-184. doi: 10.1016/j.virol.2016.07.019. [Epub ahead of print]
    Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference.

    McMillen CM1, Beezhold DH1, Blachere FM2, Othumpangat S2, Kashon ML2, Noti JD3.
    Author information

    Abstract

    Influenza antiviral drugs that use protein inhibitors can lose their efficacy as resistant strains emerge. As an alternative strategy, we investigated the use of small interfering RNA molecules (siRNAs) by characterizing three siRNAs (M747, M776 and M832) targeting the influenza matrix 2 gene and three (NS570, NS595 and NS615) targeting the nonstructural protein 1 and 2 genes. We also re-examined two previously reported siRNAs, M331 and M950, which target the matrix 1 and 2 genes. Treatment with M331-, M776-, M832-, and M950-siRNAs attenuated influenza titer. M776-siRNA treated cells had 29.8% less infectious virus than cells treated with the previously characterized siRNA, M950. NS570-, NS595- and NS615-siRNAs reduced nonstructural protein 1 and 2 expression and enhanced type I interferon expression by 50%. Combination siRNA treatment attenuated 20.9% more infectious virus than single siRNA treatment. Our results suggest a potential use for these siRNAs as an effective anti-influenza virus therapy.
    Published by Elsevier Inc.


    KEYWORDS:

    Antivirals; Gene expression; Influenza virus; Matrix protein 1 (M1); Matrix protein 2 (M2); Nonstructural protein 1 (NS1); Nonstructural protein 2 (NS2); RNA interference (RNAi); Small interfering RNA (siRNA)

    PMID: 27474950 DOI: 10.1016/j.virol.2016.07.019
    [PubMed - as supplied by publisher]
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