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.
复制标题
DOI：
10.1016/j.celrep.2023.112278
复制
发表时间：
2023-03
期刊：
影响因子：
8.8
通讯作者：
J Zhang;Erchi Zhou;Yan He;Ze-Lin Chai;Ben-Zhe Ji;Yi Tu;Hanqing Wang;Wenqiang Wu;Yong Liu;Xinghao Zhang;Yu Liu
中科院分区：
文献类型：
--
作者：
J Zhang;Erchi Zhou;Yan He;Ze-Lin Chai;Ben-Zhe Ji;Yi Tu;Hanqing Wang;Wenqiang Wu;Yong Liu;Xinghao Zhang;Yu Liu
环鸟苷单磷酸(GMP)-AMP合成酶（cGAS）作为一种关键的dsDNA识别受体，在先天免疫应答中起着至关重要的作用。激活的cGAS通过感知DNA，催化次级信使环GMP-AMP （cGAMP）的合成，cGAMP随后激活下游信号传导，诱导干扰素和炎症细胞因子的产生。在这里，我们报道了Zyg-11家族成员B （ZYG11B）在cgas介导的免疫反应中是一个有效的放大器。ZYG11B的敲低会损害cGAMP的产生和随后的干扰素和炎症细胞因子的转录。在机制上，ZYG11B增强了cGAS-DNA的结合亲和力，增强了cGAS-DNA的缩聚，稳定了cGAS-DNA缩聚复合物。此外，单纯疱疹病毒1型（HSV-1）感染诱导ZYG11B以与cgas无关的方式降解。我们的研究结果不仅揭示了ZYG11B在dna诱导的cGAS激活的早期阶段的重要作用，而且还表明了一种抑制先天免疫反应的病毒策略。
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.