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) (PMCID:PMC9119685)
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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 |
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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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