Microrna-130a Downregulates HCV Replication through an atg5-Dependent Autophagy Pathway

Xiaoqiong Duan, Xiao Liu, Wenting Li, Jacinta A. Holmes, Annie J. Kruger, Chunhui Yang, Yujia Li, Min Xu, Haiyan Ye, Shuang Li, Xinzhong Liao, Qiuju Sheng, Dong Chen, Tuo Shao, Zhimeng Cheng, Batul Kaj, Esperance A. Schaefer, Shilin Li, Limin Chen*, Wenyu LinRaymond T. Chung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We previously identified that miR-130a downregulates HCV replication through two independent pathways: Restoration of host immune responses and regulation of pyruvate metabolism. In this study, we further sought to explore host antiviral target genes regulated by miR-130a. We performed a RT2 Profiler™ PCR array to identify the host antiviral genes regulated by miR-130a. The putative binding sites between miR-130a and its downregulated genes were predicted by miRanda. miR-130a and predicted target genes were over-expressed or knocked down by siRNA or CRISPR/Cas9 gRNA. Selected gene mRNAs and their proteins, together with HCV replication in JFH1 HCV-infected Huh7.5.1 cells were monitored by qRT-PCR andWestern blot. We identified 32 genes that were significantly differentially expressed more than 1.5-fold following miR-130a overexpression, 28 of which were upregulated and 4 downregulated. We found that ATG5, a target gene for miR-130a, significantly upregulated HCV replication and downregulated interferon stimulated gene expression. miR-130a downregulated ATG5 expression and its conjugation complex with ATG12. ATG5 and ATG5-ATG12 complex affected interferon stimulated gene (ISG) such as MX1 and OAS3 expression and subsequently HCV replication. We concluded that miR-130a regulates host antiviral response and HCV replication through targeting ATG5 via the ATG5-dependent autophagy pathway.

Original languageEnglish (US)
Article number338
JournalCells
Volume8
Issue number4
DOIs
StatePublished - Apr 2019
Externally publishedYes

Keywords

  • ATG12
  • Autophagy
  • Autophagy-related genes 5 (ATG5)
  • Hepatitis C virus (HCV)
  • Interferon stimulated gene (ISG)
  • MiR-130a

ASJC Scopus subject areas

  • Medicine(all)

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