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Published on: January 9, 2019
Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain
Changqing Yu1, Yuanzhe Bai2, Wenbo Tan3
1Engineering Center of Agricultural Biosafety Assessment and Biotechnology, School of Advanced Agricultural Sciences, Yibin Vocational and Technical College, Yibin, People's Republic of China.
Abstract:
Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed 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-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is verified 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 mammalian origins showed a relatively conserved feature in blocking EBOV GP cleavage, which could provide clues for subsequent MARCHs antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.
Insights
Membrane-associated RING-CH (MARCH) proteins 1 and 2 restrict Ebola virus (EBOV) by retaining EBOV glycoprotein at the trans-Golgi network. This interaction, involving the host protein furin, impairs viral infectivity and offers new antiviral strategies.
Area of Science:
- Virology
- Cell Biology
- Protein Biochemistry
Background:
- Membrane-associated RING-CH (MARCH) proteins are known to inhibit viral replication.
- MARCH8 has been previously shown to inhibit Ebola virus (EBOV) glycoprotein (GP) maturation.
Purpose of the Study:
- To investigate the antiviral activity of human MARCH1 and MARCH2 against EBOV.
- To elucidate the molecular mechanisms by which MARCH1 and MARCH2 restrict EBOV GP.
Main Methods:
- EBOV GP-pseudotyped viral infection assays.
- Cellular localization studies using immunofluorescence.
- Co-immunoprecipitation assays to study protein interactions.
- Analysis of EBOV GP proteolytic processing.
Main Results:
- Human MARCH1 and MARCH2 restrict EBOV GP-pseudotyped viral infection.
- MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reducing cell surface display and virion infectivity.
- MARCH1/2 interact with EBOV GP and the host protein furin.
- The furin P domain is recognized by MARCH1/2/8, crucial for their inhibitory function.
- Bovine MARCH2 and murine MARCH1 also inhibit EBOV GP processing.
Conclusions:
- MARCH1 and MARCH2 exhibit conserved antiviral activity against EBOV GP across mammalian species.
- The interaction with furin is critical for MARCH-mediated restriction of EBOV.
- These findings provide insights for developing novel antiviral strategies against enveloped viruses.
