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

Cellular & Molecular Immunology volume 15, pages 907–916 (2018)Cite this article

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.

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Acknowledgements

This work was supported by grants from the National Key R&D Program of China (2017YFA0505800, 2016YFA0502102), the National Natural Science Foundation of China (31630045, 31521091, 91429304 and 31671465), the Fundamental Research Funds for the Central Universities (2042017kf0205, 2042017kf0242) and Wuhan University Experiment Technology Project Funding.

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  1. College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan, 430072, China, Hubei

    Ying Liu, Qian Zhou, Li Zhong, Heng Lin, Ming-Ming Hu, Yan Zhou, Hong-Bing Shu & Shu Li

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  1. Ying Liu
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  3. Li Zhong
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Correspondence to Yan Zhou, Hong-Bing Shu or Shu Li.

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Liu, Y., Zhou, Q., Zhong, L. et al. ZDHHC11 modulates innate immune response to DNA virus by mediating MITA–IRF3 association. Cell Mol Immunol 15, 907–916 (2018). https://doi.org/10.1038/cmi.2017.146

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