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Nat Commun. 2016 Nov 10;7:13348. doi: 10.1038/ncomms13348.

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

Author information

1
Department of Biomedicine, University of Aarhus, Bartholins Allé 6, 8000 Aarhus, Denmark.
2
Aarhus Research Center for Innate Immunology, University of Aarhus, 8000 Aarhus C, Denmark.
3
Department of Molecular Pathogenesis of Viruses, Institute of Virology, Slovak Academy of Sciences, 845 05 Bratislava, Slovak Republic.
4
Department of Infectious Diseases, Aarhus University Hospital Skejby, 8200 Aarhus N, Denmark.
5
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark.
6
Department of Clinical Medicine, University of Aarhus, 8200 Aarhus N, Denmark.
7
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

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.

PMID:
27830700
PMCID:
PMC5109551
DOI:
10.1038/ncomms13348
[Indexed for MEDLINE]
Free PMC Article

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