Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

1
Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan 430072, China.
2
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430072, China.
3
Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: shuh@whu.edu.cn.
4
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430072, China. Electronic address: wangyy@wh.iov.cn.

Abstract

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.

PMID:
25299331
DOI:
10.1016/j.chom.2014.09.006
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center