UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

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 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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