ZDHHC11 modulates innate immune response to DNA virus by mediating MITA-IRF3 association

Cell Mol Immunol. 2018 Oct;15(10):907-916. doi: 10.1038/cmi.2017.146. Epub 2018 Feb 12.

Abstract

MITA is a central adaptor in innate immune responses to DNA viruses. The mechanisms responsible for recruitment of downstream kinase TBK1 and the transcription factor IRF3 to MITA remains enigmatic. Here we identified ZDHHC11, a member of DHHC palmitoyl transferase family, as a positive regulator of DNA virus-triggered signaling. Overexpression of ZDHHC11 activated the IFN-β promoter, while ZDHHC11-deficiency specifically impaired DNA virus HSV-1-induced transcription of downstream antiviral genes. Zdhhc11-/- mice exhibited lower serum cytokine levels and higher lethality after HSV-1 infection. Mechanistically, ZDHHC11 facilitated the optimal recruitment of IRF3 to MITA. Our findings support an important role for ZDHHC11 in mediating MITA-dependent innate immune responses against DNA viruses.

Keywords: IRF3; MITA; ZDHHC11; innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology*
  • Animals
  • HEK293 Cells
  • Herpes Simplex / genetics
  • Herpes Simplex / immunology*
  • Herpes Simplex / pathology
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • THP-1 Cells

Substances

  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Membrane Proteins
  • Sting1 protein, mouse
  • Acyltransferases