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

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  • Line S Reinert
  • Katarína Lopušná, Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus C, Denmark.
  • ,
  • Henriette Winther
  • Chenglong Sun
  • ,
  • Martin K Thomsen
  • Ramya Nandakumar
  • ,
  • Trine H Mogensen
  • Morten Meyer, Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Christian Vægter
  • Jens R Nyengaard
  • Katherine A Fitzgerald, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
  • ,
  • Søren R Paludan

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.

Original languageEnglish
Article number13348
JournalNature Communications
Number of pages12
Publication statusPublished - 10 Nov 2016

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