The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling
Author:  Date:2015-11-21  Clicks:
Cell Host Microbe.2014 Oct 8;16(4):450-61. doi: 10.1016/j.chom.2014.09.006.

The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered,MITA/STING-dependent innate immune signaling.

Zhou Q 1, Lin H 1, Wang S 2, Wang S 1, Ran Y 2, Liu Y 1, Ye W 1, Xiong X 1, Zhong B 1, Shu HB 3, Wang YY 4.

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ViralDNAsensing 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 downstreamsignalingcomponents. In an expression screen for proteins that can activate the IFNB1 promoter, we identified theER-associatedproteinZDHHC1as apositiveregulatorofvirus-triggered,MITA/STING-dependentimmunesignaling.Zdhhc1(-/-) cells failed to effectively produce IFNs and other cytokines in response to infection withDNAbut not RNA viruses.Zdhhc1(-/-) mice infected with the neurotropicDNAvirus HSV-1 exhibited lower cytokine levels and higher virus titers in the brain, resulting in higher lethality.ZDHHC1constitutively associated withMITA/STING and mediates dimerization/aggregation ofMITA/STING and recruitment of the downstreamsignalingcomponents TBK1 and IRF3. These findings support a role forZDHHC1in mediatingMITA/STING-dependentinnateimmuneresponse againstDNAviruses.

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