Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association

文献类型： 外文期刊

第一作者： Zhu, Lin

作者： Zhu, Lin;Gao, Ting;Jin, Yanwen;Li, Ping;Hu, Yong;Liu, Hainan;Dong, Qincai;Wang, Guangfei;Zheng, Tong;Song, Caiwei;Liu, Xuan;Cao, Cheng;Huang, Yi;Zhang, Leike;Wu, Yan;Xiao, Gengfu;Jin, Jing;Wang, Di;Bai, Yu;Zhang, Xun;Liu, Yaoning;Yang, Weihong;Xu, Ke;Zou, Gang;Zhao, Lei;Cao, Ruiyuan;Zhong, Wu;Xia, Xianzhu

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：17.694； 五年影响因子：17.763 ）

ISSN：

年卷期： 2022 年 13 卷 1 期

页码：

收录情况： SCI

摘要： Ebola virus (EBOV), one of the deadliest viruses, is the cause of fatal Ebola virus disease (EVD). The underlying mechanism of viral replication and EBOV-related hemorrhage is not fully understood. Here, we show that EBOV VP35, a cofactor of viral RNA-dependent RNA polymerase, binds human A kinase interacting protein (AKIP1), which consequently activates protein kinase A (PKA) and the PKA-downstream transcription factor CREB1. During EBOV infection, CREB1 is recruited into EBOV ribonucleoprotein complexes in viral inclusion bodies (VIBs) and employed for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. Meanwhile, the transcription of several coagulation-related genes, including THBD and SERPINB2, is substantially upregulated by VP35-dependent CREB1 activation, which may contribute to EBOV-related hemorrhage. The finding that EBOV VP35 hijacks the host PKA-CREB1 signal axis for viral replication and pathogenesis provides novel potential therapeutic approaches against EVD. Ebola virus virion protein 35 (VP35) is a cofactor of the viral RNA-dependent RNA polymerase, required for viral assembly and IFN antagonist. Here, Zhu et al. provide evidence that EBOV VP35 induces an AKIP1-mediated (human A kinase interacting protein) activation of the PKA-CREB1 signaling pathway and contributes to viral replication and pathogenesis in vitro and in vivo.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序