UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

11-10-2016

Document Type

Article

Disciplines

Immunology and Infectious Disease | Nervous System Diseases | Virus Diseases

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.

Rights and Permissions

Copyright © 2016, The Author(s). Citation: Nat Commun. 2016 Nov 10;7:13348. doi: 10.1038/ncomms13348. Link to article on publisher's site

DOI of Published Version

10.1038/ncomms13348

Related Resources

Link to Article in PubMed

Keywords

Glial biology, Infectious diseases, Interferons, Viral host response

Journal/Book/Conference Title

Nature communications

PubMed ID

27830700

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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