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The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity
Joint Authors
Feld, Jordan J.
McGilvray, Ian D.
Lin, Liang-Tzung
Chen, Limin
Li, Yujia
Ma, Max Xuezhong
Qin, Bo
Richardson, Christopher D.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-18
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Li, Yujia& Ma, Max Xuezhong& Qin, Bo& Lin, Liang-Tzung& Richardson, Christopher D.& Feld, Jordan J.…[et al.]. 2019. The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1192765
Modern Language Association (MLA)
Li, Yujia…[et al.]. The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity. Mediators of Inflammation No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1192765
American Medical Association (AMA)
Li, Yujia& Ma, Max Xuezhong& Qin, Bo& Lin, Liang-Tzung& Richardson, Christopher D.& Feld, Jordan J.…[et al.]. The Ubiquitin-Specific Protease 18 Promotes Hepatitis C Virus Production by Increasing Viral Infectivity. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1192765
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192765