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

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


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 cell-based 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-7b-mediated suppression of HCV RNA accumulation was not dependent on inhibition of HCV translation. Let-7b and IFN alpha-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
Issue number15
StatePublished - Aug 2012


  • microRNA; Let-7b; HCV

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