The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Adenovirus Detection by the cGAS/STING/TBK1 DNA Sensing Cascade
Open accessAbstract
Adenovirus (Ad) infection triggers a cell-specific antiviral response following exposure of viral DNA to the intracellular compartment. A variety of DNA sensors (DAI, AIM2, DDx41, RNA polymerase [Pol] III, and IFI16 [p204]) have been identified in recent years; however, the DNA sensor involved in detection of adenovirus has not been established. Cyclic GMP-AMP synthase (cGAS), a DNA sensor that produces a cyclic guanine-adenine dinucleotide (cGAMP) inducer of STING, has been examined to determine its role in generating an antiadenoviral response. Short hairpin RNA (shRNA) lentiviral vectors targeting TBK1, STING, and cGAS were established in murine MS1 endothelial and RAW 264.7 macrophage cell lines. Knockdown of TBK1, STING, and cGAS results in a dramatic reduction in the activation of the primary antiviral response marker phosphorylated interferon (IFN) response factor 3 (IRF3) following exposure to adenovirus. Furthermore, activation of secondary type I IFN signaling targets ( ptyr STAT1 and ptyr STAT2 [ ptyr STAT1/2]) was also compromised. Consistent with compromised activation of primary and secondary response markers, transcriptional activation of IRF3-responsive genes (beta IFN [IFN-β], ISG15, ISG54) and secondary response transcripts were diminished in cells knocked down in cGAS, STING, or TBK1. These data establish cGAS as the dominant cytosolic DNA sensor responsible for detection of internalized adenovirus leading to induction of the type I interferon antiviral cascade.
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Cites
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
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“STING (7, 8) functions as an adaptor linking DNA recognition signaling to activation of the TBK1 kinase.”
BackgroundCGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695
STING is a direct innate immune sensor of cyclic di-GMP
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The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
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Cited by
Human chimeric antigen receptor macrophages for cancer immunotherapy
Klichinsky, M., Ruella, M., Shestova, O., Lu, X. M., Best, A., Zeeman, M., Schmierer, M., Gabrusiewicz, K., Anderson, N. R., Petty, N. E., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0462-y · Cited by 1,495
STING: infection, inflammation and cancer.
Barber, G. N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3921 · Cited by 1,313
The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
Cai, X., Chiu, Y.-H., & Chen, Z. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.040 · Cited by 988
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.78 · Cited by 593
Chen, M., Meng, Q., Qin, Y., Liang, P., Tan, P., He, L., Zhou, Y., Chen, Y., Huang, J., Wang, R.-F., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.08.025 · Cited by 367
Metadata
- Authors
- Lam, E., Stein, S., & Falck-Pedersen, E.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2014-01-15
- Volume
- 88
- Issue
- 2
- Pages
- 974-981
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2134167421
- Cited by
- 224
- References
- 8
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- green
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