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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
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机构:
Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Lin, Heng
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Wang, Suyun
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机构:
Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Wang, Shuai
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机构:
Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Ran, Yong
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Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Liu, Ying
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Ye, Wen
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Xiong, Xiaozhe
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Zhong, Bo
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Shu, Hong-Bing
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Wang, Yan-Yi
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h-index: 0
机构:
Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China
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
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.
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页码:450 / 461
页数:12
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Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Dublin 2, Ireland Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark

Fitzgerald, Katherine A.
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Univ Massachusetts, Div Infect Dis & Immunol, Dept Med, Sch Med, Worcester, MA 01605 USA Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark

Paludan, Soren R.
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Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark
Aarhus Univ, Aarhus Res Ctr Innate Immunol, DK-8000 Aarhus C, Denmark Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark