TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction

Galão, R. P., Wilson, H., Schierhorn, K. L., Debeljak, F., Bodmer, B. S., Goldhill, D., Hoenen, T., Wilson, S. J. , Swanson, C. M. and Neil, S. J. D. (2022) TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. PLoS Pathogens, 18(5), e1010530. (doi: 10.1371/journal.ppat.1010530) (PMID:35533151)

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Abstract

Ebola virus (EBOV) causes highly pathogenic disease in primates. Through screening a library of human interferon-stimulated genes (ISGs), we identified TRIM25 as a potent inhibitor of EBOV transcription-and-replication-competent virus-like particle (trVLP) propagation. TRIM25 overexpression inhibited the accumulation of viral genomic and messenger RNAs independently of the RNA sensor RIG-I or secondary proinflammatory gene expression. Deletion of TRIM25 strongly attenuated the sensitivity of trVLPs to inhibition by type-I interferon. The antiviral activity of TRIM25 required ZAP and the effect of type-I interferon was modulated by the CpG dinucleotide content of the viral genome. We find that TRIM25 interacts with the EBOV vRNP, resulting in its autoubiquitination and ubiquitination of the viral nucleoprotein (NP). TRIM25 is recruited to incoming vRNPs shortly after cell entry and leads to dissociation of NP from the vRNA. We propose that TRIM25 targets the EBOV vRNP, exposing CpG-rich viral RNA species to restriction by ZAP.

Item Type:Articles
Additional Information:These studies were funded by an MRC Discovery Award MC/PC/15068 and a Wellcome Trust Senior Research Fellowship (WT098049AIA) to SJDN, an MRC research grant MR/S000844/1 and a Guy’s and St Thomas’s Charity Challenge Fund grant to CMS and SJDN, and MRC research grant MR/M019756/1 to CMS. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 750621 (KLS). Additional funding was provided by the Friedrich-Loeffler-Institut as intramural funding (TH) and funding as part of the VISION consortium (BSB).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson, Professor Sam
Creator Roles:
Wilson, S. J.Conceptualization, Funding acquisition, Investigation, Methodology, Writing – review and editing
Authors: Galão, R. P., Wilson, H., Schierhorn, K. L., Debeljak, F., Bodmer, B. S., Goldhill, D., Hoenen, T., Wilson, S. J., Swanson, C. M., and Neil, S. J. D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Published Online:09 May 2022
Copyright Holders:Copyright © 2022 Galão et al.
First Published:First published in PLoS Pathogens 18(5): e1010530
Publisher Policy:Reproduced under a Creative Commons License

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