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Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS

Author

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  • Line S. Reinert

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

  • Katarína Lopušná

    (University of Aarhus
    Institute of Virology, Slovak Academy of Sciences)

  • Henriette Winther

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

  • Chenglong Sun

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

  • Martin K. Thomsen

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

  • Ramya Nandakumar

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

  • Trine H. Mogensen

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus
    Aarhus University Hospital Skejby)

  • Morten Meyer

    (Institute of Molecular Medicine, University of Southern Denmark)

  • Christian Vægter

    (University of Aarhus)

  • Jens R. Nyengaard

    (University of Aarhus)

  • Katherine A. Fitzgerald

    (University of Massachusetts Medical School)

  • Søren R. Paludan

    (University of Aarhus
    Aarhus Research Center for Innate Immunology, University of Aarhus)

Abstract

Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS–STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS–STING pathway orchestrates an antiviral program that includes type I IFNs and immune-priming of other cell types.

Suggested Citation

  • Line S. Reinert & Katarína Lopušná & Henriette Winther & Chenglong Sun & Martin K. Thomsen & Ramya Nandakumar & Trine H. Mogensen & Morten Meyer & Christian Vægter & Jens R. Nyengaard & Katherine A. F, 2016. "Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13348
    DOI: 10.1038/ncomms13348
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    Cited by:

    1. Xintao Tu & Ting-Ting Chu & Devon Jeltema & Kennady Abbott & Kun Yang & Cong Xing & Jie Han & Nicole Dobbs & Nan Yan, 2022. "Interruption of post-Golgi STING trafficking activates tonic interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Stéphanie Bibert & Mathieu Quinodoz & Sylvain Perriot & Fanny S. Krebs & Maxime Jan & Rita C. Malta & Emilie Collinet & Mathieu Canales & Amandine Mathias & Nicole Faignart & Eliane Roulet-Perez & Pas, 2024. "Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Qiu Pan & Yan Xie & Ying Zhang & Xinqi Guo & Jing Wang & Min Liu & Xiao-Lian Zhang, 2024. "EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Meihua Jin & Hiroki Shiwaku & Hikari Tanaka & Takayuki Obita & Sakurako Ohuchi & Yuki Yoshioka & Xiaocen Jin & Kanoh Kondo & Kyota Fujita & Hidenori Homma & Kazuyuki Nakajima & Mineyuki Mizuguchi & Hi, 2021. "Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.

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