Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity
- PMID: 28132838
- DOI: 10.1016/j.chom.2017.01.001
Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity
Abstract
Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex. UL82 also impaired the recruitment of TBK1 and IRF3 to the STING complex. The levels of downstream antiviral genes induced by UL82-deficient HCMV were higher than those induced by wild-type HCMV. Conversely, wild-type HCMV replicated more efficiently than the UL82-deficient mutant. These findings reveal an important mechanism of immune evasion by HCMV.
Keywords: HCMV; MITA; STING; UL82; cGAS; iRhom2; immune evasion; innate immunity; virus.
Copyright © 2017 Elsevier Inc. All rights reserved.
Similar articles
-
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.
-
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 DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3- and NF-κB-Mediated Transcription.J Virol. 2019 May 15;93(11):e00181-19. doi: 10.1128/JVI.00181-19. Print 2019 Jun 1. J Virol. 2019. PMID: 30867312 Free PMC article.
-
The human cytomegalovirus tegument protein pp65 (pUL83): a key player in innate immune evasion.New Microbiol. 2018 Apr;41(2):87-94. Epub 2018 Jan 31. New Microbiol. 2018. PMID: 29384558 Review.
-
The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus.J Mol Biol. 2013 Dec 13;425(24):4857-71. doi: 10.1016/j.jmb.2013.08.023. Epub 2013 Sep 5. J Mol Biol. 2013. PMID: 24013068 Free PMC article. Review.
Cited by
-
Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins.Signal Transduct Target Ther. 2021 Mar 15;6(1):123. doi: 10.1038/s41392-021-00515-5. Signal Transduct Target Ther. 2021. PMID: 33723219 Free PMC article.
-
Protein S-Nitrosylation of Human Cytomegalovirus pp71 Inhibits Its Ability To Limit STING Antiviral Responses.J Virol. 2020 Aug 17;94(17):e00033-20. doi: 10.1128/JVI.00033-20. Print 2020 Aug 17. J Virol. 2020. PMID: 32581105 Free PMC article.
-
ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response.Nat Commun. 2018 Aug 22;9(1):3349. doi: 10.1038/s41467-018-05559-w. Nat Commun. 2018. PMID: 30135424 Free PMC article.
-
P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response.Appl Microbiol Biotechnol. 2023 Oct;107(20):6277-6286. doi: 10.1007/s00253-023-12703-0. Epub 2023 Aug 14. Appl Microbiol Biotechnol. 2023. PMID: 37578557
-
UL88 Mediates the Incorporation of a Subset of Proteins into the Virion Tegument.J Virol. 2020 Jul 1;94(14):e00474-20. doi: 10.1128/JVI.00474-20. Print 2020 Jul 1. J Virol. 2020. PMID: 32376624 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
