Yonsei Med J.  2018 Dec;59(10):1181-1189. 10.3349/ymj.2018.59.10.1181.

Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5

• Gong W
• Guo X
• Zhang Y

• KMID: 2426332
• DOI: http://doi.org/10.3349/ymj.2018.59.10.1181

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.

Keyword

Hepatitis C virus; replication; miR-373; IRF5; type 1 IFN

MeSH Terms

Biopsy
Blotting, Western
Hepacivirus*
Hepatitis C*
Hepatitis*
Interferons*
Liver
Liver Diseases
Luciferases
MicroRNAs
Polymerase Chain Reaction
Reverse Transcription
RNA
Interferons
Luciferases
MicroRNAs
RNA