IFI16 is an innate immune sensor for intracellular DNA
Open accessAbstract
The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
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IFI16 is a DNA sensor and effector of innate immune responses during viral infection, detecting viral DNA in both nucleus and cytoplasm.
“For instance, the DNA sensor IFI16 is an effector of innate immune responses during viral infection, detecting viral DNA in both the nucleus and the cytoplasm (71–73, 136, 137).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [137]
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- Authors
- Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., Fitzgerald, K. A., Paludan, S. R., & Bowie, A. G.
- Affiliations
- Trinity College Dublin (IE)
- Aarhus University (DK)
- University of Massachusetts Chan Medical School (US)
- National Institutes of Health (US)
- University of Bonn (DE)
- Corresponding author
- Bowie, Andrew G
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-10-03
- Volume
- 11
- Issue
- 11
- Pages
- 997-1004
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3142795
- OpenAlex
- W2131617804
- Cited by
- 1,643
- References
- 42
- Citations by year
- 2026: 51 · 2025: 88 · 2024: 104 · 2023: 73 · 2022: 104 · 2021: 113 · 2020: 102 · 2019: 115 · 2018: 114 · 2017: 93 · 2016: 100 · 2015: 124 · 2014: 125 · 2013: 133 · 2012: 97
- FWCI
- 45.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- HAL (submittedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, cc-by-nc-sa)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI067497)
- University of Miami
- Sundhed og Sygdom, Det Frie Forskningsråd (09-072636)
- York University
- Science Foundation Ireland (07/IN.1/B934)
- Trinity College Dublin
- Lundbeckfonden (R17-2007-1526, R34-2009-3855)
- University of Toronto
- H. Lundbeck A/S
- National Institutes of Health (AI067497, AI067497 to K.A.F)
- Medical Research Council
- National Heart, Lung, and Blood Institute (R01HL093262)
- National Institute of Allergy and Infectious Diseases (R01AI067497, R37AI067497, R01 AI083641, AI083713, AI-067497, R01AI083713, R56AI067497)
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- IFI16, AIM2-like receptors, innate immunity, interferon-beta induction, STING, TBK1, IRF3, NF-κB, herpes simplex virus type 1, P204
- MeSH terms
- STING Protein, Animals, Cell Line, DNA-Binding Proteins, DNA, Viral, Humans, Immunity, Innate, Membrane Proteins, Monocytes, Nuclear Proteins, Phosphoproteins, Signal Transduction, Interferon-beta, Herpesvirus 1, Human, Intracellular Space, Mice
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