Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5.
10.3349/ymj.2018.59.10.1181
- Author:
Weifeng GONG
1
;
Xiaobo GUO
;
Yangmin ZHANG
Author Information
1. Department of Blood Transfusion, Xi'an Central Hospital, Xi'an, China. qianl4587963@sina.com
- Publication Type:Original Article
- Keywords:
Hepatitis C virus;
replication;
miR-373;
IRF5;
type 1 IFN
- MeSH:
Biopsy;
Blotting, Western;
Hepacivirus*;
Hepatitis C*;
Hepatitis*;
Interferons*;
Liver;
Liver Diseases;
Luciferases;
MicroRNAs;
Polymerase Chain Reaction;
Reverse Transcription;
RNA
- From:Yonsei Medical Journal
2018;59(10):1181-1189
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Hepatitis C virus (HCV) poses a risk of chronic liver disease and threatens a significant number of people worldwide. MicroRNAs (miRNAs) are linked to the regulation of hepatocarcinogenesis. Although miR-373 is required for HCV infection, the underlying mechanisms of miR-373 involvement in HCV replication remain elusive. MATERIALS AND METHODS: Quantitative reverse transcription PCR assays were performed to detect the abundances of miR-373 and HCV RNA either in Huh 7.5 cells or liver biopsy specimens with HCV infection. Luciferase assay was employed to probe the interactions between miR-373 and interferon regulatory factor 5 (IRF5). Western blot was conducted to investigate the effect of miR-373 and IRF5 on HCV replication and activation of type 1 interferon (IFN) response in JFH1-infected Huh 7.5 cells. RESULTS: HCV infection appeared to be caused by increased miR-373 expression. Addition of miR-373 promoted HCV RNA expression, while miR-373 depletion led to an inhibitive effect on HCV replication. Concordantly, IRF5, as a direct target, was limited by miR-373 in JFH1-infected Huh 7.5 cells. In addition, introduction of IRF5 protected HCV replication in the presence of abundant miR-373. Furthermore, the miR-373-mediated inhibitory effect on type 1 IFN response was ablated following IRF5 accumulation. CONCLUSION: miR-373 abrogation reduced HCV replication via activation of type 1 IFN responses by targeting IRF5 in JFH1-infected Huh 7.5 cells, suggesting a promising therapeutic for treating HCV infection.
