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

被引：120

作者：

Lian, Huan ^{[1
]}

Wei, Jin ^{[1
]}

Zang, Ru ^{[1
]}

Ye, Wen ^{[1
]}

Yang, Qing ^{[1
]}

Zhang, Xia-Nan ^{[1
,2
]}

Chen, Yun-Da ^{[1
,2
]}

Fu, Yu-Zhi ^{[3
]}

Hu, Ming-Ming ^{[1
]}

Lei, Cao-Qi ^{[1
,2
]}

Luo, Wei-Wei ^{[3
]}

Li, Shu ^{[1
]}

Shu, Hong-Bing ^{[1
,2
]}

机构：

[1] Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Hubei, Peoples R China

[2] Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China

[3] Chinese Acad Sci, Wuhan Inst Virol, Wuhan 430071, Hubei, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

CYCLIC GMP-AMP; CYTOSOLIC DNA SENSOR; INTRACELLULAR DNA; DENDRITIC CELLS; MYCOBACTERIUM-TUBERCULOSIS; ANTIVIRAL RESPONSE; I INTERFERONS; ADAPTER; SYNTHASE; 2ND-MESSENGER;

D O I：

10.1038/s41467-018-05559-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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