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Human MARCH1, 2, and 8 Block Ebola Virus Envelope Glycoprotein Cleavage via Targeting Furin P Domain
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  • Chunfu Zheng,
  • Changqing Yu,
  • Wenbo Tan,
  • Yu Bai,
  • Yulong Zhou,
  • Jinbo Zhai,
  • Mengzhou Xue,
  • Qiang Liu
Chunfu Zheng
Guangdong Academy of Agricultural Sciences

Corresponding Author:[email protected]

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Changqing Yu
Yibin Vocational and Technical College
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Wenbo Tan
Heilongjiang University
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Yu Bai
Wenzhou Vocational College of Science and Technology
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Yulong Zhou
Heilongjiang Bayi Agricultural University
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Jinbo Zhai
Universities of Inner Mongolia Autonomous Region
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Mengzhou Xue
The Second Affiliated Hospital of Zhengzhou University
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Qiang Liu
Nanchong Vocational and Technical College
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Membrane-Associated Ring-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes of action. Previous work proved that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-mediated viral replication. Human MARCH1 and MARCH2 retain EBOV GP in the trans-Golgi network (TGN), reduce its surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase (PC) furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is confirmed to be recognized by MARCH1/2/8, which is critical for their blocking activities. Besides, bovine MARCH2 and murine MARCH1 also impair EBOV GP proteolytic processing. Altogether, our findings confirm that MARCH1/2 proteins of different species showed a relatively conserved feature in blocking EBOV GP proteolytic processing, which could provide a reference for subsequent antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.
10 May 2023Submitted to Journal of Medical Virology
10 May 2023Submission Checks Completed
10 May 2023Assigned to Editor
10 May 2023Review(s) Completed, Editorial Evaluation Pending
12 May 2023Reviewer(s) Assigned
08 Jun 2023Editorial Decision: Revise Major
01 Sep 20231st Revision Received
04 Sep 2023Submission Checks Completed
04 Sep 2023Assigned to Editor
04 Sep 2023Review(s) Completed, Editorial Evaluation Pending
06 Sep 2023Reviewer(s) Assigned
11 Nov 2023Editorial Decision: Revise Minor