Let-7b is a novel regulator of hepatitis C virus replication

Ju Chien Cheng*, Yung Ju Yeh, Ching Ping Tseng, Sheng Da Hsu, Yu Ling Chang, Naoya Sakamoto, Hsien Da Huang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

106 Scopus citations

Abstract

The non-coding microRNA (miRNA) is involved in the regulation of hepatitis C virus (HCV) infection and offers an alternative target for developing anti-HCV agent. In this study, we aim to identify novel cellular miRNAs that directly target the HCV genome with anti-HCV therapeutic potential. Bioinformatic analyses were performed to unveil liver-abundant miRNAs with predicted target sequences on HCV genome. Various cellbased systems confirmed that let-7b plays a negative role in HCV expression. In particular, let-7b suppressed HCV replicon activity and down-regulated HCV accumulation leading to reduced infectivity of HCVcc. Mutational analysis identified let-7b binding sites at the coding sequences of NS5B and 5′-UTR of HCV genome that were conserved among various HCV genotypes. We further demonstrated that the underlying mechanism for let-7bmediated suppression of HCV RNA accumulation was not dependent on inhibition of HCV translation. Let-7b and IFNα-2a also elicited a synergistic inhibitory effect on HCV infection. Together, let-7b represents a novel cellular miRNA that targets the HCV genome and elicits anti-HCV activity. This study thereby sheds new insight into understanding the role of host miRNAs in HCV pathogenesis and to developing a potential anti-HCV therapeutic strategy.

Original languageEnglish
Pages (from-to)2621-2633
Number of pages13
JournalCellular and Molecular Life Sciences
Volume69
Issue number15
DOIs
StatePublished - 08 2012

Keywords

  • HCV
  • Let-7b
  • MicroRNA

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