Send to

Choose Destination
See comment in PubMed Commons below
J Hepatol. 2009 Mar;50(3):453-60. doi: 10.1016/j.jhep.2008.06.010. Epub 2008 Jul 9.

Regulation of the hepatitis C virus genome replication by miR-199a.

Author information

Center for Genomic Medicine, Kyoto University, Shogoin-Kawaharacho, Kyoto, Japan.



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.


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.


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.


The results of this study suggest that miR-199a directly regulates HCV replication and may serve as a novel antiviral therapy.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center