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

Nature Communications
Huan LianHong-Bing Shu

Abstract

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.

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Citations

Dec 13, 2018·Nature Communications·Sulayman BenmerzougValerie F J Quesniaux
Dec 13, 2019·Experimental & Molecular Medicine·Hyun-Cheol LeeJong-Soo Lee
Dec 5, 2019·Annual Review of Immunology·Ming-Ming Hu, Hong-Bing Shu
Mar 6, 2020·Journal of Molecular Cell Biology·Ru ZangHong-Bing Shu
Apr 19, 2020·Cellular and Molecular Life Sciences : CMLS·Uri Aceituno-ValenzuelaMaría Rosa Ponce
Aug 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yong RanYan-Yi Wang
May 1, 2020·Cell Discovery·Li ZhongHong-Bing Shu
Jul 31, 2019·Nature Reviews. Genetics·Mona MotwaniKatherine A Fitzgerald
Aug 8, 2019·Cellular & Molecular Immunology·Xuan ZhongHong-Bing Shu
Jul 24, 2019·Frontiers in Immunology·Na LiJin-Lian Hua
Apr 30, 2020·Molecular & Cellular Proteomics : MCP·Bokai SongIleana M Cristea
May 18, 2020·Cellular & Molecular Immunology·Chen-Yang LiaoHong-Bing Shu
Oct 28, 2020·International Journal of Molecular Sciences·Yakun Wu, Shitao Li
May 20, 2020·Nature Reviews. Molecular Cell Biology·Karl-Peter Hopfner, Veit Hornung
Dec 5, 2020·Nature Communications·Xiaona SunJunjie Zhang
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Bokai SongIleana M Cristea
Mar 24, 2020·Biochemical and Biophysical Research Communications·Peng GaoHong-Bing Shu
Mar 7, 2021·Journal of Clinical Medicine·Kennedy C Ukadike, Tomas Mustelin
Nov 7, 2020·EMBO Reports·Jonny Hertzog, Jan Rehwinkel
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May 1, 2021·Signal Transduction and Targeted Therapy·Le Yu, Pengda Liu
Apr 29, 2021·Cell Discovery·Li ZhongHong-Bing Shu

Methods Mentioned

BETA
transfection
ELISA
co-immunoprecipitation
confocal microscopy
proximity
pull-down
Microscale thermophoresis
Assay
electrophoresis

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