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
  • 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: [email protected].
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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