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Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses

Author

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  • Miyu Moriyama

    (The University of Tokyo
    Fukuoka University
    Yale University School of Medicine)

  • Takumi Koshiba

    (Fukuoka University)

  • Takeshi Ichinohe

    (The University of Tokyo)

Abstract

Cytosolic mitochondrial DNA (mtDNA) activates cGAS-mediated antiviral immune responses, but the mechanism by which RNA viruses stimulate mtDNA release remains unknown. Here we show that viroporin activity of influenza virus M2 or encephalomyocarditis virus (EMCV) 2B protein triggers translocation of mtDNA into the cytosol in a MAVS-dependent manner. Although influenza virus-induced cytosolic mtDNA stimulates cGAS- and DDX41-dependent innate immune responses, the nonstructural protein 1 (NS1) of influenza virus associates with mtDNA to evade the STING-dependent antiviral immunity. The STING-dependent antiviral signaling is amplified in neighboring cells through gap junctions. In addition, we find that STING-dependent recognition of influenza virus is essential for limiting virus replication in vivo. Our results show a mechanism by which influenza virus stimulates mtDNA release and highlight the importance of DNA sensing pathway in limiting influenza virus replication.

Suggested Citation

  • Miyu Moriyama & Takumi Koshiba & Takeshi Ichinohe, 2019. "Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12632-5
    DOI: 10.1038/s41467-019-12632-5
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    Cited by:

    1. Nathan Meade & Helen K. Toreev & Ram P. Chakrabarty & Charles R. Hesser & Chorong Park & Navdeep S. Chandel & Derek Walsh, 2023. "The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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