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Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein
- Source :
- Cell Host & Microbe. 18:333-344
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- SummaryInvading 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 binding and DNA binding. Moreover, ORF52 homologs 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.
- Subjects :
- chemistry.chemical_classification
Cancer Research
ATP synthase
viruses
virus diseases
Signal transducing adaptor protein
biochemical phenomena, metabolism, and nutrition
Biology
Nucleotidyltransferase
Microbiology
Molecular biology
3. Good health
Cell biology
Cytosol
chemistry.chemical_compound
Enzyme
chemistry
Cell culture
Immunology and Microbiology(all)
Virology
Second messenger system
biology.protein
Parasitology
Molecular Biology
DNA
Subjects
Details
- ISSN :
- 19313128
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Cell Host & Microbe
- Accession number :
- edsair.doi.dedup.....2541266dc7db9b5970c3eaee7b970e33