2. Academic Validation
  3. ZYG11B potentiates the antiviral innate immune response by enhancing cGAS-DNA binding and condensation

ZYG11B potentiates the antiviral innate immune response by enhancing cGAS-DNA binding and condensation

  • Cell Rep. 2023 Mar 17;42(3):112278. doi: 10.1016/j.celrep.2023.112278.
Jie Zhang 1,  Er-Chi Zhou 2,  Yan He 1,  Ze-Lin Chai 1,  Ben-Zhe Ji 1,  Yi Tu 1,  Han-Ling Wang 3,  Wen-Qiang Wu 4,  Yong Liu 1,  Xing-Hua Zhang 2,  Yu Liu 5
Affiliations

Affiliations

  • 1 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.
  • 2 College of Life Sciences, Wuhan University, Wuhan 430072, China.
  • 3 Xi'an Jiaotong-Livepool University, Suzhou 215123, China.
  • 4 College of Life Science, Henan University, Kaifeng 475001, China.
  • 5 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. Electronic address: yuliu@whu.edu.cn.
PMID: 36933219 DOI: 10.1016/j.celrep.2023.112278
Abstract

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.

Keywords

CP: Immunology; HSV-1; ZYG11B; cGAS; innate immunity; interferon.

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