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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Reinert LS,Lopušná K,Winther H,Sun C,Thomsen MK,Nandakumar R,Mogensen TH,Meyer M,Vægter C,Nyengaard JR,Fitzgerald KA,Paludan SR

doi

10.1038/ncomms13348

subject

Has Abstract

pub_date

2016-11-10 00:00:00

pages

13348

issn

2041-1723

pii

ncomms13348

journal_volume

7

pub_type

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