Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein
Ermela Paparisto,
Nina R. Hunt,
Daniel S. Labach,
Macon D. Coleman,
Eric J. Di Gravio,
Mackenzie J. Dodge,
Nicole J. Friesen,
Marceline Côté,
Andreas Müller,
Thomas Hoenen,
Stephen D. Barr
Affiliations
Ermela Paparisto
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Nina R. Hunt
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Daniel S. Labach
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Macon D. Coleman
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Eric J. Di Gravio
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Mackenzie J. Dodge
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Nicole J. Friesen
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Marceline Côté
Department of Biochemistry, Microbiology, and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Roger-Guindon Hall Room 4214, Ottawa, ON K1H 8M5 , Canada
Andreas Müller
Friedrich-Loeffler-Institut, Institute of Molecular Virology and Cell Biology, Südufer 10, 17493 Greifswald—Insel Riems, Germany
Thomas Hoenen
Friedrich-Loeffler-Institut, Institute of Molecular Virology and Cell Biology, Südufer 10, 17493 Greifswald—Insel Riems, Germany
Stephen D. Barr
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel ‘protagonist–antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.
