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Science: Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

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  • Science: Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

    Science. 2016 Apr 22;352(6284):463-6. doi: 10.1126/science.aaf3926.
    Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease.

    Pillai PS1, Molony RD1, Martinod K2, Dong H1, Pang IK1, Tal MC1, Solis AG1, Bielecki P1, Mohanty S3, Trentalange M4, Homer RJ5, Flavell RA6, Wagner DD2, Montgomery RR7, Shaw AC3, Staeheli P8, Iwasaki A9.
    Author information



    Abstract

    Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the in vivo consequence, we used mice expressing a functional Mx gene encoding a major interferon-induced effector against IAV in humans. In Mx1-intact mice with weakened resistance due to deficiencies in Mavs and Tlr7, we found an elevated respiratory bacterial burden. Notably, mortality in the absence of Mavs and Tlr7 was independent of viral load or MyD88-dependent signaling but dependent on bacterial burden, caspase-1/11, and neutrophil-dependent tissue damage. Therefore, in the context of weakened antiviral resistance, vulnerability to IAV disease is a function of caspase-dependent pathology.
    Copyright ? 2016, American Association for the Advancement of Science.


    PMID: 27102485 [PubMed - in process]
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