ZYG11B potentiates the antiviral innate immune response by enhancing cGAS-DNA binding and condensation
Jie Zhang,
Er-Chi Zhou,
Yan He,
Ze-Lin Chai,
Ben-Zhe Ji,
Yi Tu,
Han-Ling Wang,
Wen-Qiang Wu,
Yong Liu,
Xing-Hua Zhang,
Yu Liu
Affiliations
Jie Zhang
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Er-Chi Zhou
College of Life Sciences, Wuhan University, Wuhan 430072, China
Yan He
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Ze-Lin Chai
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Ben-Zhe Ji
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Yi Tu
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Han-Ling Wang
Xi’an Jiaotong-Livepool University, Suzhou 215123, China
Wen-Qiang Wu
College of Life Science, Henan University, Kaifeng 475001, China
Yong Liu
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China
Xing-Hua Zhang
College of Life Sciences, Wuhan University, Wuhan 430072, China
Yu Liu
State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China; College of Life Sciences, Wuhan University, Wuhan 430072, China; Corresponding author
Summary: As a key dsDNA recognition receptor, cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) plays a vital role in innate immune responses. Activated cGAS, by sensing DNA, catalyzes the synthesis of the secondary messenger cyclic GMP-AMP (cGAMP), which subsequently activates downstream signaling to induce production of interferons and inflammatory cytokines. Here, we report Zyg-11 family member B (ZYG11B) as a potent amplifier in cGAS-mediated immune responses. Knockdown of ZYG11B impairs production of cGAMP and subsequent transcription of interferon and inflammatory cytokines. Mechanistically, ZYG11B enhances cGAS-DNA binding affinity, potentiates cGAS-DNA condensation, and stabilizes the cGAS-DNA condensed complex. Moreover, herpes simplex virus 1 (HSV-1) infection induces ZYG11B degradation in a cGAS-unrelated manner. Our findings not only reveal an important role of ZYG11B in the early stage of DNA-induced cGAS activation but also indicate a viral strategy to dampen the innate immune response.
