The ER-Associated Protein ZDHHC1 Is a Positive Regulator of DNA Virus-Triggered, MITA/STING-Dependent Innate Immune Signaling

被引：134

作者：

Zhou, Qian ^{[1
]}

Lin, Heng ^{[1
]}

Wang, Suyun ^{[2
]}

Wang, Shuai ^{[1
]}

Ran, Yong ^{[2
]}

Liu, Ying ^{[1
]}

Ye, Wen ^{[1
]}

Xiong, Xiaozhe ^{[1
]}

Zhong, Bo ^{[1
]}

Shu, Hong-Bing ^{[1
]}

Wang, Yan-Yi ^{[2
]}

机构：

[1] Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

[2] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430072, Peoples R China

来源：

CELL HOST & MICROBE | 2014年 / 16卷 / 04期

基金：

中国国家自然科学基金;

关键词：

CYCLIC GMP-AMP; CYTOSOLIC DNA; ENDOPLASMIC-RETICULUM; INTRACELLULAR DNA; ANTIVIRAL RESPONSE; DENDRITIC CELLS; NUCLEIC-ACIDS; RECOGNITION; PATHWAY; ADAPTER;

D O I：

10.1016/j.chom.2014.09.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Viral DNA sensing within the cytosol of infected cells activates type I interferon (IFN) expression. MITA/STING plays an essential role in this pathway by acting as both a sensor for the second messenger cGAMP and as an adaptor for downstream signaling components. In an expression screen for proteins that can activate the IFNB1 promoter, we identified the ER-associated protein ZDHHC1 as a positive regulator of virus-triggered, MITA/STING-dependent immune signaling. Zdhhc1(-/-) cells failed to effectively produce IFNs and other cytokines in response to infection with DNA but not RNA viruses. Zdhhc1(-/-) mice infected with the neurotropic DNA virus HSV-1 exhibited lower cytokine levels and higher virus titers in the brain, resulting in higher lethality. ZDHHC1 constitutively associated with MITA/STING and mediates dimerization/aggregation of MITA/STING and recruitment of the downstream signaling components TBK1 and IRF3. These findings support a role for ZDHHC1 in mediating MITA/STING-dependent innate immune response against DNA viruses.

引用

页码：450 / 461

页数：12

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