Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS
AuthorsReinert, Line S.
Thomsen, Martin K.
Mogensen, Trine H.
Nyengaard, Jens R.
Fitzgerald, Katherine A.
Paludan, Soren R.
UMass Chan AffiliationsDivision of Infectious Diseases and Immunology, Department of Medicine
Viral host response
Immunology and Infectious Disease
Nervous System Diseases
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AbstractHerpes 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.
SourceNat Commun. 2016 Nov 10;7:13348. doi: 10.1038/ncomms13348. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40197
Related ResourcesLink to Article in PubMed
RightsCopyright © 2016, The Author(s).