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ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response

Nature communications, 2018-08, Vol.9 (1), p.3349-13, Article 3349 [Peer Reviewed Journal]

2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2018. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2018, corrected publication 2021 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-018-05559-w ;PMID: 30135424

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Title:
ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response
Author: Lian, Huan ; Wei, Jin ; Zang, Ru ; Ye, Wen ; Yang, Qing ; Zhang, Xia-Nan ; Chen, Yun-Da ; Fu, Yu-Zhi ; Hu, Ming-Ming ; Lei, Cao-Qi ; Luo, Wei-Wei ; Li, Shu ; Shu, Hong-Bing
Subjects: AMP ; Animals ; Binding ; Chemical synthesis ; Cyclic GMP ; Cytosol ; Deoxyribonucleic acid ; DNA ; DNA - genetics ; DNA - metabolism ; DNA viruses ; Herpes simplex ; Immune response ; Immune system ; Immunity, Innate - genetics ; Immunity, Innate - physiology ; Infections ; Innate immunity ; Mice ; Mice, Knockout ; Nucleotides, Cyclic - metabolism ; Nucleotidyltransferases - genetics ; Nucleotidyltransferases - metabolism ; Proteins ; Recognition ; RNA Nucleotidyltransferases - genetics ; RNA Nucleotidyltransferases - metabolism ; Signal Transduction - genetics ; Signal Transduction - physiology ; Viral infections ; Viruses ; Zinc ; Zinc finger proteins
Is Part Of: Nature communications, 2018-08, Vol.9 (1), p.3349-13, Article 3349
Description: Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-018-05559-w
PMID: 30135424
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

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ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response

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