ZDHHC11 modulates innate immune response to DNA virus by mediating MITA-IRF3 association
ZDHHC11 modulates innate immune response to DNA virus by mediating MITA-IRF3 association
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ZDHHC11 通过介导 MITA-IRF3 关联来调节对 DNA 病毒的先天免疫反应
DOI：
10.1038/cmi.2017.146
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发表时间：
2018-10-01
影响因子：
24.1
通讯作者：
Li, Shu
中科院分区：
文献类型：
--
作者：
Liu, Ying;Zhou, Qian;Li, Shu
MITA是对DNA病毒的先天免疫反应中的一个中央适配器。下游激酶TBK1和转录因子IRF3向MITA募集的机制仍然是个谜。在这里，我们发现DHHC棕榈酰转移酶家族的成员ZDHHC11是DNA病毒触发信号的正调控因子。ZDHHC11的过表达激活了干扰素-β启动子，而ZDHHC11的缺失则特异性地削弱了DNA病毒HSV-1诱导的下游抗病毒基因的转录。Zdhhc11(-/-)小鼠感染HSV-1后，血清细胞因子水平降低，致死率升高。从机制上讲，ZDHHC11促进了IRF3向MITA的最佳招募。我们的发现支持了ZDHHC11在介导MITA依赖的针对DNA病毒的先天免疫反应中的重要作用。
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-beta 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.