Human
MARCH1, 2, and 8 Block Ebola Virus Envelope Glycoprotein Cleavage via
Targeting Furin P Domain
Changqing Yu 1
#, Wenbo Tan 4#, Yu Bai 5#,
Yulong Zhou 8,
Jingbo Zhai 6, Mengzhou Xue 7,
Chunfu Zheng 2,9*, Qiang Liu 3*
1 Egineering
Center of Agricultural Biosafety Assessment and Biotechnology, School of
Advanced Agricultural Sciences, Yibin Vocational and Technical College,
Yibin, People’s Republic of China;
2 Institute of Animal Health, Guangdong Academy of
Agricultural Sciences, Key Laboratory of Livestock Disease Prevention of
Guangdong Province, Scientific Observation and Experiment Station of
Veterinary Drugs and Diagnostic Techniques of Guangdong Province,
Ministry of Agriculture and Rural Affairs, Guangzhou, People’s Republic
of China;
3 Nanchong Key Laboratory of Disease Prevention,
Control and Detection in Livestock and Poultry, Nanchong Vocational and
Technical College, Nanchong, People’s Republic of China;
4 College of
Advanced Agriculture and Ecological Environment, Heilongjiang
University, Harbin, People’s Republic of China;
5 College of
Animal Science, Wenzhou Vocational College of Science and Technology,
Wenzhou, People’s Republic of China;
6 Key
Laboratory of Zoonose Prevention and Control at Universities of Inner
Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu
University, Tongliao, People’s Republic of China;
7 Department of Cerebrovascular Diseases, The Second
Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou,
Henan, People’s Republic of China;
8 College of
Animal Science and Technology, Heilongjiang Bayi Agricultural
University, Daqing, People’s Republic of China;
9 Department of
Microbiology, Immunology & Infection Diseases, University of Calgary,
Calgary, Alberta, Canada.
# These authors contributed equally to this work.
* Correspondence
Chunfu Zheng,
zheng.alan@hotmail.com
Qiang Liu,
liuqiang_yyy@163.com
Abstract: 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.