Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion
- PMID: 29937271
- DOI: 10.1016/j.chom.2018.05.007
Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion
Abstract
The cytosolic DNA sensor cGAS recognizes viral DNA and synthesizes the second messenger cGAMP upon viral infection. cGAMP binds to the adaptor protein MITA/STING to activate downstream signaling events, leading to induction of type I interferons (IFNs) and antiviral effector genes. Here we identify the human cytomegalovirus (HCMV) protein UL31 as an inhibitor of cGAS. UL31 interacts directly with cGAS and disassociates DNA from cGAS, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. UL31 overexpression markedly reduces antiviral responses stimulated by cytosolic DNA, while knockdown or knockout of UL31 heightens HCMV-triggered induction of type I IFNs and downstream antiviral genes. Moreover, wild-type HCMV replicates more efficiently than UL31-deficient HCMV, a phenotype that is reversed in cGAS null cells. These results highlight the importance of cGAS in the host response to HCMV as well as an important viral strategy to evade this innate immune sensor.
Keywords: UL31; cGAS; human cytomegalovirus; immune evasion; type I interferons.
Copyright © 2018 Elsevier Inc. All rights reserved.
Similar articles
-
Conserved strategies for pathogen evasion of cGAS-STING immunity.Curr Opin Immunol. 2020 Oct;66:27-34. doi: 10.1016/j.coi.2020.04.002. Epub 2020 Apr 15. Curr Opin Immunol. 2020. PMID: 32339908 Free PMC article. Review.
-
Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I Interferon Production by Inactivating the DNA Sensor cGAS without Affecting STING.J Virol. 2018 Feb 26;92(6):e01774-17. doi: 10.1128/JVI.01774-17. Print 2018 Mar 15. J Virol. 2018. PMID: 29263269 Free PMC article.
-
Human cytomegalovirus protein UL42 antagonizes cGAS/MITA-mediated innate antiviral response.PLoS Pathog. 2019 May 20;15(5):e1007691. doi: 10.1371/journal.ppat.1007691. eCollection 2019 May. PLoS Pathog. 2019. PMID: 31107917 Free PMC article.
-
Human Cytomegalovirus Protein UL94 Targets MITA to Evade the Antiviral Immune Response.J Virol. 2020 Jun 1;94(12):e00022-20. doi: 10.1128/JVI.00022-20. Print 2020 Jun 1. J Virol. 2020. PMID: 32238587 Free PMC article.
-
cGAS-cGAMP-STING: The three musketeers of cytosolic DNA sensing and signaling.IUBMB Life. 2016 Nov;68(11):858-870. doi: 10.1002/iub.1566. Epub 2016 Oct 5. IUBMB Life. 2016. PMID: 27706894 Review.
Cited by
-
Regulation of cGAS/STING signaling and corresponding immune escape strategies of viruses.Front Cell Infect Microbiol. 2022 Sep 14;12:954581. doi: 10.3389/fcimb.2022.954581. eCollection 2022. Front Cell Infect Microbiol. 2022. PMID: 36189363 Free PMC article. Review.
-
cGAMP-activated cGAS-STING signaling: its bacterial origins and evolutionary adaptation by metazoans.Nat Struct Mol Biol. 2023 Mar;30(3):245-260. doi: 10.1038/s41594-023-00933-9. Epub 2023 Mar 9. Nat Struct Mol Biol. 2023. PMID: 36894694 Review.
-
Viral dUTPases: Modulators of Innate Immunity.Biomolecules. 2022 Jan 28;12(2):227. doi: 10.3390/biom12020227. Biomolecules. 2022. PMID: 35204728 Free PMC article. Review.
-
African Swine Fever Virus Armenia/07 Virulent Strain Controls Interferon Beta Production through the cGAS-STING Pathway.J Virol. 2019 May 29;93(12):e02298-18. doi: 10.1128/JVI.02298-18. Print 2019 Jun 15. J Virol. 2019. PMID: 30918080 Free PMC article.
-
Conserved strategies for pathogen evasion of cGAS-STING immunity.Curr Opin Immunol. 2020 Oct;66:27-34. doi: 10.1016/j.coi.2020.04.002. Epub 2020 Apr 15. Curr Opin Immunol. 2020. PMID: 32339908 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
