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

Published:28 March 2023 DOI: 10.1016/j.celrep.2023.112278 PMID: 36933219
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

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.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
Fluorescein isothiocyanate 27072-45-3 C21H11NO5S 303 suppliers $18.00-$2676.00
Fluorescein isothiocyanate 27072-45-3 C21H11NO5S 303 suppliers $18.00-$2676.00
Fluorescein isothiocyanate 27072-45-3 C21H11NO5S 303 suppliers $18.00-$2676.00
Fluorescein isothiocyanate 27072-45-3 C21H11NO5S 303 suppliers $18.00-$2676.00
5(6)-Carboxytetramethylrhodamine N-succinimidyl ester 246256-50-8 C29H25N307 118 suppliers Inquiry
5(6)-Carboxytetramethylrhodamine N-succinimidyl ester 246256-50-8 C29H25N307 118 suppliers Inquiry

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