The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity
Background and Aims. Ubiquitin-specific protease 18 (USP18) is involved in immunoregulation and response to interferon- (IFN-) based treatment in patients chronically infected with hepatitis C virus (HCV). We investigated whether and how its upregulation alters HCV infection. Methods. Overexpression...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/3124745 |
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| author | Yujia Li Max Xuezhong Ma Bo Qin Liang-Tzung Lin Christopher D. Richardson Jordan Feld Ian D. McGilvray Limin Chen |
| author_facet | Yujia Li Max Xuezhong Ma Bo Qin Liang-Tzung Lin Christopher D. Richardson Jordan Feld Ian D. McGilvray Limin Chen |
| author_sort | Yujia Li |
| collection | DOAJ |
| description | Background and Aims. Ubiquitin-specific protease 18 (USP18) is involved in immunoregulation and response to interferon- (IFN-) based treatment in patients chronically infected with hepatitis C virus (HCV). We investigated whether and how its upregulation alters HCV infection. Methods. Overexpression of wild-type (USP18 WT) or catalytically inactive mutant (USP18 C64S) USP18 was examined for effects on HCV replication in the absence and presence of IFNα or IFNλ using both the HCV-infective model and replicon cells. The IFN signaling pathway was assessed via STAT1 phosphorylation (western blot) and downstream ISG expression (real-time PCR). Mechanistic roles were sought by quantifying microRNA-122 levels and J6/JFH1 infectivity of Huh7.5 cells. Results. We found that overexpression of either USP18 WT or USP18 C64S stimulated HCV production and blunted the anti-HCV effect of IFNα and IFNλ in the infective model but not in the replicon system. Overexpressed USP18 showed no effect on Jak/STAT signaling nor on microRNA-122 expression. However, USP18 upregulation markedly increased J6/JFH1 infectivity and promoted the expression of the key HCV entry factor CD81 on Huh7.5 cells. Conclusions. USP18 stimulates HCV production and blunts the effect of both type I and III IFNs by fostering a cellular environment characterized by upregulation of CD81, promoting virus entry and infectivity. |
| format | Article |
| id | doaj-art-71f1809ba6bc4bbb9c6e1b880d2944e2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-71f1809ba6bc4bbb9c6e1b880d2944e22025-02-03T06:08:30ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/31247453124745The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral InfectivityYujia Li0Max Xuezhong Ma1Bo Qin2Liang-Tzung Lin3Christopher D. Richardson4Jordan Feld5Ian D. McGilvray6Limin Chen7Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Peking Union Medical College, Chengdu, Sichuan 610052, ChinaToronto General Research Institute, University of Toronto, Toronto, Ontario, M5S 1A1, CanadaDepartment of Infectious Diseases, The 1st Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanDepartment of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, CanadaToronto General Research Institute, University of Toronto, Toronto, Ontario, M5S 1A1, CanadaToronto General Research Institute, University of Toronto, Toronto, Ontario, M5S 1A1, CanadaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences, Peking Union Medical College, Chengdu, Sichuan 610052, ChinaBackground and Aims. Ubiquitin-specific protease 18 (USP18) is involved in immunoregulation and response to interferon- (IFN-) based treatment in patients chronically infected with hepatitis C virus (HCV). We investigated whether and how its upregulation alters HCV infection. Methods. Overexpression of wild-type (USP18 WT) or catalytically inactive mutant (USP18 C64S) USP18 was examined for effects on HCV replication in the absence and presence of IFNα or IFNλ using both the HCV-infective model and replicon cells. The IFN signaling pathway was assessed via STAT1 phosphorylation (western blot) and downstream ISG expression (real-time PCR). Mechanistic roles were sought by quantifying microRNA-122 levels and J6/JFH1 infectivity of Huh7.5 cells. Results. We found that overexpression of either USP18 WT or USP18 C64S stimulated HCV production and blunted the anti-HCV effect of IFNα and IFNλ in the infective model but not in the replicon system. Overexpressed USP18 showed no effect on Jak/STAT signaling nor on microRNA-122 expression. However, USP18 upregulation markedly increased J6/JFH1 infectivity and promoted the expression of the key HCV entry factor CD81 on Huh7.5 cells. Conclusions. USP18 stimulates HCV production and blunts the effect of both type I and III IFNs by fostering a cellular environment characterized by upregulation of CD81, promoting virus entry and infectivity.http://dx.doi.org/10.1155/2019/3124745 |
| spellingShingle | Yujia Li Max Xuezhong Ma Bo Qin Liang-Tzung Lin Christopher D. Richardson Jordan Feld Ian D. McGilvray Limin Chen The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity Mediators of Inflammation |
| title | The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity |
| title_full | The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity |
| title_fullStr | The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity |
| title_full_unstemmed | The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity |
| title_short | The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity |
| title_sort | ubiquitin specific protease 18 promotes hepatitis c virus production by increasing viral infectivity |
| url | http://dx.doi.org/10.1155/2019/3124745 |
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