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

Author

Listed:
  • Lin Zhu

    (Beijing Institute of Biotechnology)

  • Ting Gao

    (Beijing Institute of Biotechnology)

  • Yi Huang

    (National Biosafety Laboratory, Chinese Academy of Sciences)

  • Jing Jin

    (Anhui University)

  • Di Wang

    (Anhui University)

  • Leike Zhang

    (National Biosafety Laboratory, Chinese Academy of Sciences)

  • Yanwen Jin

    (Beijing Institute of Biotechnology)

  • Ping Li

    (Beijing Institute of Biotechnology)

  • Yong Hu

    (Beijing Institute of Biotechnology)

  • Yan Wu

    (National Biosafety Laboratory, Chinese Academy of Sciences)

  • Hainan Liu

    (Beijing Institute of Biotechnology)

  • Qincai Dong

    (Beijing Institute of Biotechnology)

  • Guangfei Wang

    (Beijing Institute of Biotechnology)

  • Tong Zheng

    (Beijing Institute of Biotechnology)

  • Caiwei Song

    (Beijing Institute of Biotechnology)

  • Yu Bai

    (Anhui University)

  • Xun Zhang

    (Anhui University)

  • Yaoning Liu

    (Anhui University)

  • Weihong Yang

    (Anhui University)

  • Ke Xu

    (Wuhan University)

  • Gang Zou

    (Insitut Pasteur of Shanghai, Chinese Academy of Sciences)

  • Lei Zhao

    (Beijing Institute of Pharmacology and Toxicology)

  • Ruiyuan Cao

    (Beijing Institute of Pharmacology and Toxicology)

  • Wu Zhong

    (Beijing Institute of Pharmacology and Toxicology)

  • Xianzhu Xia

    (Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences)

  • Gengfu Xiao

    (National Biosafety Laboratory, Chinese Academy of Sciences)

  • Xuan Liu

    (Beijing Institute of Biotechnology)

  • Cheng Cao

    (Beijing Institute of Biotechnology)

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.

Suggested Citation

  • 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 & , 2022. "Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29948-4
    DOI: 10.1038/s41467-022-29948-4
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    Cited by:

    1. Jingru Fang & Guillaume Castillon & Sebastien Phan & Sara McArdle & Chitra Hariharan & Aiyana Adams & Mark H. Ellisman & Ashok A. Deniz & Erica Ollmann Saphire, 2023. "Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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