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Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation

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  • Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation

    Antiviral Res. 2019 Aug 27;171:104593. doi: 10.1016/j.antiviral.2019.104593. [Epub ahead of print]
    Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation.

    Bavagnoli L1, Campanini G2, Forte M1, Ceccotti G1, Percivalle E2, Bione S1, Lisa A1, Baldanti F2, Maga G3.
    Author information

    1 Institute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, 27100, Pavia, Italy. 2 Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy. 3 Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy. Electronic address: giovanni.maga@igm.cnr.it.

    Abstract

    The influenza A virus (IAV) NS1 protein is one of the major regulators of pathogenicity, being able to suppress innate immune response and host protein synthesis. In this study we identified the human micro RNA hsa-miR-1307-3p as a novel potent suppressor of NS1 expression and influenza virus replication. Transcriptomic analysis indicates that hsa-miR-1307-3p also negatively regulates apoptosis and promotes cell proliferation. In addition, we identified a novel mutation in the NS1 gene of A(H1N1)pdm09 strains circulating in Italy in the 2010-11 season, which enabled the virus to escape the hsa-miR-1307-3p inhibition, conferring replicative advantage to the virus in human cells. To the best of our knowledge, this is the first validation of suppression of IAV H1N1 NS1 by a human micro RNA and the first example of an escape mutation from micro RNA-mediated antiviral response for the A(H1N1)pdm09 virus.
    Copyright ? 2019 The Authors. Published by Elsevier B.V. All rights reserved.


    KEYWORDS:

    Antiviral micro-RNA; Escape mutation; Host-pathogen interaction; Human influenza a virus; Influenza pandemics

    PMID: 31470040 DOI: 10.1016/j.antiviral.2019.104593
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