期刊
CELL HOST & MICROBE
卷 16, 期 4, 页码 450-461出版社
CELL PRESS
DOI: 10.1016/j.chom.2014.09.006
关键词
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资金
- Ministry of Science and Technology of China [2010CB911802, 2012CB910201, 2014CB542603]
- National Natural Science Foundation of China [31221061, 31321001, 31270932, 31130020, 91029302, 31371427]
- 10,000 Talents Plan
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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