@article{880f77317f7e4644be9d4cff22803690,
title = "TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction",
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.",
author = "{Ribeiro Galao}, {Rui Pedro} and Harry Wilson and Kristina Schierhorn and Franka Debeljak and Bianca Bodmer and Daniel Goldhill and Thomas Hoenen and Wilson, {Sam J.} and Chad Swanson and Stuart Neil",
note = "Funding 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{\textquoteright}s and St Thomas{\textquoteright}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{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank other members of the Neil and Swanson laboratories for helpful discussions and Wendy S Barclay (Imperial College London) for materials. We are grateful to Stefan Becker and his group, as well as Adam Fletcher for advice. Publisher Copyright: Copyright: {\textcopyright} 2022 Gal{\~a}o et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2022",
month = may,
day = "19",
doi = "10.1371/journal.ppat.1010530",
language = "English",
volume = "18",
journal = "Plos pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "5",
}
