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Πέμπτη 26 Ιανουαρίου 2017

Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity

Publication date: Available online 26 January 2017
Source:Cell Host & Microbe
Author(s): Yu-Zhi Fu, Shan Su, Yi-Qun Gao, Pei-Pei Wang, Zhe-Fu Huang, Ming-Ming Hu, Wei-Wei Luo, Shu Li, Min-Hua Luo, Yan-Yi Wang, Hong-Bing Shu
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.

Graphical abstract

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Teaser

Whether and how HCMV proteins target the host immune system for evasion is enigmatic. Fu et al. found that HCMV protein UL82 inhibits STING-mediated signaling by impairing its cellular trafficking and complex formation, leading to inhibition of innate antiviral response and immune evasion by HCMV.


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