title: 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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China 430072.
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Fu
authors.affiliation: Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan, China 430071.
authors.forename: Shan
authors.initials: S
authors.lastname: Su
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China 430072.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Gao
authors.affiliation: Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan, China 430071.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 430071.
authors.forename: Zhe-Fu
authors.initials: ZF
authors.lastname: Huang
authors.affiliation: Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan, China 430071.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Hu
authors.affiliation: Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan, China 430071.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China 430072.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 430071.
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Luo
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 430071.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China 430072; Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan, China 430071. Electronic address: shuh@whu.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000099197:STING Protein
chemical_list: D050838:Interferon Regulatory Factor-3; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D014764:Viral Proteins; C494232:IRF3 protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C051298:cytomegalovirus phosphoprotein 71kDa; C403191:TBK1 protein, human
keywords: HCMV; MITA; STING; UL82; cGAS; iRhom2; immune evasion; innate immunity; virus