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

Cell Host Microbe. 2014 Oct 8;16(4):450-61. doi: 10.1016/j.chom.2014.09.006.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Animals
  • Brain / pathology
  • Brain / virology
  • Cell Line
  • Cytokines / analysis
  • Disease Models, Animal
  • Encephalitis, Herpes Simplex / immunology
  • Encephalitis, Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Immunity, Innate*
  • Interferon-beta / biosynthesis*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Signal Transduction*
  • Survival Analysis
  • Viral Load


  • Cytokines
  • Membrane Proteins
  • STING1 protein, human
  • Interferon-beta
  • Acyltransferases
  • ZDHHC1 protein, human