2. Academic Validation
  3. Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association

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

  • Nat Commun. 2022 Apr 26;13(1):2256. doi: 10.1038/s41467-022-29948-4.
Lin Zhu  # 1,  Ting Gao  # 1,  Yi Huang  # 2,  Jing Jin 3,  Di Wang 3,  Leike Zhang 2,  Yanwen Jin 1,  Ping Li 1,  Yong Hu 1,  Yan Wu 2,  Hainan Liu 1,  Qincai Dong 1,  Guangfei Wang 1,  Tong Zheng 1,  Caiwei Song 1,  Yu Bai 3,  Xun Zhang 3,  Yaoning Liu 3,  Weihong Yang 3,  Ke Xu 4,  Gang Zou 5,  Lei Zhao 6,  Ruiyuan Cao 6,  Wu Zhong 6,  Xianzhu Xia 7,  Gengfu Xiao 8,  Xuan Liu 9,  Cheng Cao 10
Affiliations

Affiliations

  • 1 Beijing Institute of Biotechnology, Beijing, 100039, China.
  • 2 National Biosafety Laboratory, Chinese Academy of Sciences, Wuhan, Hubei, 430020, China.
  • 3 Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China.
  • 4 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
  • 5 Insitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 6 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • 7 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, China.
  • 8 National Biosafety Laboratory, Chinese Academy of Sciences, Wuhan, Hubei, 430020, China. [email protected].
  • 9 Beijing Institute of Biotechnology, Beijing, 100039, China. [email protected].
  • 10 Beijing Institute of Biotechnology, Beijing, 100039, China. [email protected].
  • # Contributed equally.
PMID: 35474062 DOI: 10.1038/s41467-022-29948-4
Abstract

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.

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