Author(s): Murakami Y, Aly HH, Tajima A, Inoue I, Shimotohno K
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Abstract BACKGROUND/AIMS: Hepatitis C virus (HCV) infection causes chronic hepatitis and hepatocellular carcinoma. Current anti-HCV therapies are based on interferon therapy, which is insufficiently effective. microRNAs (miRNAs) are non-coding RNAs that regulate gene expression, and they have recently been shown to play an important role in viral replication. METHODS: An algorithm-based search for miRNAs that target the HCV genome yielded one miRNA, miR-199a, with a sequence similar to the HCV genome that is conserved among HCV genotypes. RESULTS: Over expression of miR-199a inhibited HCV genome replication in two cells bearing replicons (replicon cell) HCV-1b or -2a, however, miRNA inhibition by specific antisense oligonucleotide (ASO) accelerated viral replication. Prior transfection of immortalized hepatocytes which were infected with serum of HCV genotype 1b and 2a-infected patients, with miR-199a reduced HCV RNA replication activity. Mutation in the miR-199a target site in the replicon reduced the effect of the miR-199a. HCV replicon RNA is accumulated to the RNA-induced silencing complex (RISC) when miR-199a was over-expressed to the replicon cell. This antiviral effect by miR-199a was independent of the interferon pathway. CONCLUSIONS: The results of this study suggest that miR-199a directly regulates HCV replication and may serve as a novel antiviral therapy.
This article was published in J Hepatol
and referenced in Journal of Antivirals & Antiretrovirals