TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.
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 inhibite...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010530 |
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| _version_ | 1850162835985793024 |
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| author | Rui Pedro Galão Harry Wilson Kristina L Schierhorn Franka Debeljak Bianca S Bodmer Daniel Goldhill Thomas Hoenen Sam J Wilson Chad M Swanson Stuart J D Neil |
| author_facet | Rui Pedro Galão Harry Wilson Kristina L Schierhorn Franka Debeljak Bianca S Bodmer Daniel Goldhill Thomas Hoenen Sam J Wilson Chad M Swanson Stuart J D Neil |
| author_sort | Rui Pedro Galão |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-34a54108f0ea4e32a9ec38404b2b6055 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-34a54108f0ea4e32a9ec38404b2b60552025-08-20T02:22:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-05-01185e101053010.1371/journal.ppat.1010530TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.Rui Pedro GalãoHarry WilsonKristina L SchierhornFranka DebeljakBianca S BodmerDaniel GoldhillThomas HoenenSam J WilsonChad M SwansonStuart J D NeilEbola 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.https://doi.org/10.1371/journal.ppat.1010530 |
| spellingShingle | Rui Pedro Galão Harry Wilson Kristina L Schierhorn Franka Debeljak Bianca S Bodmer Daniel Goldhill Thomas Hoenen Sam J Wilson Chad M Swanson Stuart J D Neil TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. PLoS Pathogens |
| title | TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. |
| title_full | TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. |
| title_fullStr | TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. |
| title_full_unstemmed | TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. |
| title_short | TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction. |
| title_sort | trim25 and zap target the ebola virus ribonucleoprotein complex to mediate interferon induced restriction |
| url | https://doi.org/10.1371/journal.ppat.1010530 |
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