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Interferon-independent STING signaling promotes resistance to HSV-1 in vivo

Author

Listed:
  • Lívia H. Yamashiro

    (University of California
    University of California)

  • Stephen C. Wilson

    (University of California
    Bristol Myers Squibb)

  • Huntly M. Morrison

    (University of California)

  • Vasiliki Karalis

    (University of California)

  • Jing-Yi J. Chung

    (University of California)

  • Katherine J. Chen

    (University of California)

  • Helen S. Bateup

    (University of California
    University of California
    Chan Zuckerberg Biohub)

  • Moriah L. Szpara

    (Pennsylvania State University)

  • Angus Y. Lee

    (University of California)

  • Jeffery S. Cox

    (University of California
    University of California)

  • Russell E. Vance

    (University of California
    University of California
    University of California
    University of California)

Abstract

The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA. To initiate signaling, serine 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I interferons (IFNs). Additionally, evolutionary conserved responses such as autophagy also occur downstream of STING, but their relative importance during in vivo infections remains unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) mutation in STING are unexpectedly resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT, suggesting that the STING CTT initiates protective responses against HSV-1, independently of type I IFNs. Interestingly, we find that STING-induced autophagy is a CTT- and TBK1-dependent but IRF3-independent process that is conserved in the STING S365A mice. Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in vivo.

Suggested Citation

  • Lívia H. Yamashiro & Stephen C. Wilson & Huntly M. Morrison & Vasiliki Karalis & Jing-Yi J. Chung & Katherine J. Chen & Helen S. Bateup & Moriah L. Szpara & Angus Y. Lee & Jeffery S. Cox & Russell E. , 2020. "Interferon-independent STING signaling promotes resistance to HSV-1 in vivo," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17156-x
    DOI: 10.1038/s41467-020-17156-x
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    Cited by:

    1. Mutian Jia & Yuanyuan Wang & Jie Wang & Danhui Qin & Mengge Wang & Li Chai & Yue Fu & Chunyuan Zhao & Chengjiang Gao & Jihui Jia & Wei Zhao, 2023. "Myristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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