Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Interferon-induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein

Nina R Hunt
,
Ermela Paparisto
,
Daniel S Labach
,
Macon D Coleman
,
Eric J Di Gravio
,
Mackenzie J Dodge
,
Marceline Côté
ORCID logo ,
Andreas Müller
,
Thomas Hoenen
ORCID logo ,
Stephen D Barr
* ORCID logo
Version 1 : Received: 29 April 2021 / Approved: 30 April 2021 / Online: 30 April 2021 (15:44:44 CEST)

A peer-reviewed article of this Preprint also exists.

Paparisto, E.; Hunt, N.R.; Labach, D.S.; Coleman, M.D.; Di Gravio, E.J.; Dodge, M.J.; Friesen, N.J.; Côté, M.; Müller, A.; Hoenen, T.; Barr, S.D. Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein. Cells 2021, 10, 2399. Paparisto, E.; Hunt, N.R.; Labach, D.S.; Coleman, M.D.; Di Gravio, E.J.; Dodge, M.J.; Friesen, N.J.; Côté, M.; Müller, A.; Hoenen, T.; Barr, S.D. Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein. Cells 2021, 10, 2399.

Abstract

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 identifies 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.

Keywords

Ebola Virus, Marburg Virus, HERC5, Antiviral, Interferon

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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