The PRMT5/WDR77 complex restricts hepatitis E virus replication.
Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011434 |
| _version_ | 1797688361324904448 |
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| author | Xiaohui Ju Yanying Yu Wenlin Ren Lin Dong Xianbin Meng Haiteng Deng Yuchen Nan Qiang Ding |
| author_facet | Xiaohui Ju Yanying Yu Wenlin Ren Lin Dong Xianbin Meng Haiteng Deng Yuchen Nan Qiang Ding |
| author_sort | Xiaohui Ju |
| collection | DOAJ |
| description | Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host factors associated with HEV ORF1 protein, which were putatively responsible for viral genomic RNA replication, in these two cell culture models. Of note, the protein arginine methyltransferase 5 (PRMT5)/WDR77 complex was identified in both cell culture models as the top hit. Furthermore, we demonstrated that PRMT5 and WDR77 can specifically inhibit HEV replication, but not other viruses such as HCV or SARS-CoV-2, and this inhibition is conserved among different HEV strains and genotypes. Mechanistically, PRMT5/WDR77 can catalyse methylation of ORF1 on its R458, impairing its replicase activity, and virus bearing R458K mutation in ORF1 relieves the restriction of PRMT5/WDR77 accordingly. Taken together, our study promotes more comprehensive understanding of viral infections but also provides therapeutic targets for intervention. |
| first_indexed | 2024-03-12T01:30:06Z |
| format | Article |
| id | doaj.art-49f91b1ab2194daeaa5135c61bd4225b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-12T01:30:06Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-49f91b1ab2194daeaa5135c61bd4225b2023-09-12T05:31:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-06-01196e101143410.1371/journal.ppat.1011434The PRMT5/WDR77 complex restricts hepatitis E virus replication.Xiaohui JuYanying YuWenlin RenLin DongXianbin MengHaiteng DengYuchen NanQiang DingHepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host factors associated with HEV ORF1 protein, which were putatively responsible for viral genomic RNA replication, in these two cell culture models. Of note, the protein arginine methyltransferase 5 (PRMT5)/WDR77 complex was identified in both cell culture models as the top hit. Furthermore, we demonstrated that PRMT5 and WDR77 can specifically inhibit HEV replication, but not other viruses such as HCV or SARS-CoV-2, and this inhibition is conserved among different HEV strains and genotypes. Mechanistically, PRMT5/WDR77 can catalyse methylation of ORF1 on its R458, impairing its replicase activity, and virus bearing R458K mutation in ORF1 relieves the restriction of PRMT5/WDR77 accordingly. Taken together, our study promotes more comprehensive understanding of viral infections but also provides therapeutic targets for intervention.https://doi.org/10.1371/journal.ppat.1011434 |
| spellingShingle | Xiaohui Ju Yanying Yu Wenlin Ren Lin Dong Xianbin Meng Haiteng Deng Yuchen Nan Qiang Ding The PRMT5/WDR77 complex restricts hepatitis E virus replication. PLoS Pathogens |
| title | The PRMT5/WDR77 complex restricts hepatitis E virus replication. |
| title_full | The PRMT5/WDR77 complex restricts hepatitis E virus replication. |
| title_fullStr | The PRMT5/WDR77 complex restricts hepatitis E virus replication. |
| title_full_unstemmed | The PRMT5/WDR77 complex restricts hepatitis E virus replication. |
| title_short | The PRMT5/WDR77 complex restricts hepatitis E virus replication. |
| title_sort | prmt5 wdr77 complex restricts hepatitis e virus replication |
| url | https://doi.org/10.1371/journal.ppat.1011434 |
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