The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein
Open accessAbstract
SUMMARY Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimulate production of type I interferons (IFNs). Although several DNA viruses are sensed by cGAS, viral strategies targeting cGAS are virtually unknown. We report here that Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, an abundant gammaherpesvirus-specific tegument protein, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS- and DNA-binding. Moreover, ORF52 homologues in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA, suggesting conserved inhibitory mechanisms. Furthermore, KSHV infection evokes cGAS-dependent responses that can limit the infection, and an ORF52-null mutant exhibits increased cGAS signaling. Our findings reveal a mechanism through which gammaherpesviruses antagonize host cGAS DNA sensing.
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Cites
Identification of Herpesvirus-Like DNA Sequences in AIDS-Sssociated Kaposi's Sarcoma
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
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Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
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Self-citationA diverse range of gene products are effectors of the type I interferon antiviral response
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AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
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Self-citationCGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
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STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway
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Cited by
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293
Cesarman, E., Damania, B., Krown, S. E., Martin, J., Bower, M., & Whitby, D. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0060-9 · Cited by 697
Self-citationDNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway
Lau, L., Gray, E. E., Brunette, R. L., & Stetson, D. B. (2015) · Science · doi:10.1126/science.aab3291 · Cited by 453
The cGAS-STING Defense Pathway and Its Counteraction by Viruses
Ma, Z., & Damania, B. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.010 · Cited by 445
Metadata
- Authors
- Wu, J.-J., Li, W., Shao, Y., Avey, D., Fu, B., Gillen, J., Hand, T., Ma, S., Liu, X., Miley, W., Konrad, A., Neipel, F., Stürzl, M., Whitby, D., Li, H., & Zhu, F.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 18
- Issue
- 3
- Pages
- 333-344
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2114085082
- Cited by
- 278
- References
- 67
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wu, J.-J., Li, W., Shao, Y., Avey, D., Fu, B., Gillen, J., Hand, T., Ma, S., Liu, X., Miley, W., Konrad, A., Neipel, F., Stürzl, M., Whitby, D., Li, H., & Zhu, F. (2015). Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2015.07.015
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