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Cited by 397interferon and immune responsesHerpesvirus Infections and TreatmentsNeuroinflammation and Neurodegeneration Mechanisms

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

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Reinert, Line S., Lopušná, Katarína, Winther, Henriette, Sun, Chenglong, Thomsen, Martin K., Nandakumar, Ramya, Mogensen, Trine H., Meyer, Morten +4 more·2016·Nature Communications
DOI 10.1038/ncomms13348PMC PMC5109551
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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.

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  • IFN-I is important for controlling an HSV-1 infection and reactivation in the CNS, as HSV-1 DNA is sensed by the innate immune cGAS-STING pathway in microglia, which orchestrates IFN-I production and a potent antiviral defense program.

    “IFN-I is important for controlling an HSV-1 infection and reactivation in the CNS, as HSV-1 DNA is sensed by the innate immune cGAS–STING pathway in microglia, which orchestrates IFN-I production and a potent antiviral defense program [93].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [93]

    The Results (section 'STING-dependent type I IFN production by microglia'; page not provided) show that HSV-1-infected microglia produce type I IFN through cGAS and STING. The Discussion (page not provided) describes how this response limits viral replication and spreads antiviral activity to other CNS cells. The cited passages address HSV-1 infection, but do not establish a role in controlling reactivation. (LLM, conf=0.88)

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Authors
Reinert, L. S., Lopušná, K., Winther, H., Sun, C., Thomsen, M. K., Nandakumar, R., Mogensen, T. H., Meyer, M., Vægter, C., Nyengaard, J. R., Fitzgerald, K. A., & Paludan, S. R.
Affiliations
  • Aarhus University (DK)
  • University of Southern Denmark (DK)
  • University of Massachusetts Chan Medical School (US)
Corresponding author
Paludan, Søren R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-11-10
Volume
7
Issue
1
Pages
13348-13348
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms13348
PMC
PMC5109551
OpenAlex
W2552994754
Cited by
397
References
2
Citations by year
2026: 37 · 2025: 53 · 2024: 68 · 2023: 50 · 2022: 50 · 2021: 47 · 2020: 32 · 2019: 25 · 2018: 23 · 2017: 11
FWCI
11.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (acceptedVersion, cc-by)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Aarhus Universitet
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • Villum Fonden (00008721)
  • Aarhus Universitets Forskningsfond
  • Lundbeckfonden (R108-2012-10358, R198-2015-171, R34-3855)
  • Novo Nordisk
  • Novo Nordisk Fonden (NNF13OC0006211)
  • H. Lundbeck A/S
  • Medical Research Council (EU FP7)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
herpes simplex virus type 1, herpes simplex encephalitis, cGAS-STING pathway, microglia, type I interferon, antiviral defense, central nervous system, TLR3, astrocytes, neurons, innate immunity, viral sensing
MeSH terms
STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, Antiviral Agents, Astrocytes, Cells, Cultured, Humans, Interferon Type I, Membrane Proteins, Mice, Inbred C57BL, Nucleotidyltransferases, Signal Transduction, Microglia, Herpesvirus 1, Human, Mice, Knockout, Encephalitis, Herpes Simplex, Host-Pathogen Interactions

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