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

• DOI: 10.1038/s41467-022-29948-4
• Publication Date: 2022-04-26T10:09:28Z
• Authors: Lin Zhu; Ting Gao; Yi Huang; Jing Jin; Di Wang; Leike Zhang; Yanwen Jin; Ping Li; Yong Hu; Yan Wu; Hainan Liu; Qincai Dong; Guangfei Wang; Tong Zheng; Caiwei Song; Yu Bai; Xun Zhang; Yaoning Liu; Weihong Yang; Ke Xu; Gang Zou; Lei Zhao; Ruiyuan Cao; Wu Zhong; Xianzhu Xia; Gengfu Xiao; Xuan Liu; Cheng Cao
• Keywords: Pathogenesis; Replication; CREB1

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