p53 promotes ZDHHC1-mediated IFITM3 palmitoylation to inhibit Japanese encephalitis virus replication

文献类型： 外文期刊

第一作者： Wang, Xin

作者： Wang, Xin;Liu, Shan-Lu;Wu, Zhuanchang;Li, Yuming;Yang, Yifan;Xiao, Changguang;Liu, Xiqian;Xiang, Xiao;Wei, Jianchao;Shao, Donghua;Liu, Ke;Deng, Xufang;Qiu, Yafeng;Li, Beibei;Ma, Zhiyong;Wang, Xin;Wu, Jiaqiang

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.823； 五年影响因子：7.455 ）

ISSN： 1553-7366

年卷期： 2020 年 16 卷 10 期

页码：

收录情况： SCI

摘要： Author summary The tumor suppressor p53 contributes to the host antiviral response against Japanese encephalitis virus (JEV). We explored the downstream molecules responsible for the p53-mediated anti-JEV response. p53 transcriptionally up-regulated the expression of the palmitoyltransferase zinc finger DHHC domain-containing protein 1 (ZDHHC1) to enhance stability of the antiviral restriction factor interferon-induced transmembrane protein 3 (IFITM3) by regulating its palmitoylation. Knockdown of either ZDHHC1 or IFITM3 expression compromised the anti-JEV effect of p53. These observations suggest the existence of a previously unrecognized crosstalk between p53 and IFITM3, mediated by ZDHHC1, thus revealing a novel regulatory pathway p53-ZDHHC1-IFITM3 with an essential role in the p53-mediated anti-JEV response. The tumor suppressor p53 as an innate antiviral regulator contributes to restricting Japanese encephalitis virus (JEV) replication, but the mechanism is still unclear. The interferon-induced transmembrane protein 3 (IFITM3) is an intrinsic barrier to a range of virus infection, whether IFITM3 is responsible for the p53-mediated anti-JEV response remains elusive. Here, we found that IFITM3 significantly inhibited JEV replication in a protein-palmitoylation-dependent manner and incorporated into JEV virions to diminish the infectivity of progeny viruses. Palmitoylation was also indispensible for keeping IFITM3 from lysosomal degradation to maintain its protein stability. p53 up-regulated IFITM3 expression at the protein level via enhancing IFITM3 palmitoylation. Screening of palmitoyltransferases revealed that zinc finger DHHC domain-containing protein 1 (ZDHHC1) was transcriptionally up-regulated by p53, and consequently ZDHHC1 interacted with IFITM3 to promote its palmitoylation and stability. Knockdown of IFITM3 significantly impaired the inhibitory role of ZDHHC1 on JEV replication. Meanwhile, knockdown of either ZDHHC1 or IFITM3 expression also compromised the p53-mediated anti-JEV effect. Interestingly, JEV reduced p53 expression to impair ZDHHC1 mediated IFITM3 palmitoylation for viral evasion. Our data suggest the existence of a previously unrecognized p53-ZDHHC1-IFITM3 regulatory pathway with an essential role in restricting JEV infection and provide a novel insight into JEV-host interaction.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序