A liver‐specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication
- 18 August 2011
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 25 (12), 4511-4521
- https://doi.org/10.1096/fj.11-187781
Abstract
Regulated gene expression and progeny production are essential for persistent and chronic infection by human pathogens, such as hepatitis B virus (HBV), which affects >400 million people worldwide and is a major cause of liver disease. In this study, we provide the first direct evidence that a liver-specific microRNA, miR-122, binds to a highly conserved HBV pregenomic RNA sequence via base-pairing interactions and inhibits HBV gene expression and replication. The miR-122 target sequence is located at the coding region of the mRNA for the viral polymerase and the 3' untranslated region of the mRNA for the core protein. In cultured cells, HBV gene expression and replication reduces with increased expression of miR-122, and the expression of miR-122 decreases in the presence of HBV infection and replication. Furthermore, analyses of clinical samples demonstrated an inverse linear correlation in vivo between the miR-122 level and the viral loads in the peripheral blood mononuclear cells of HBV-positive patients. Our results suggest that miR-122 may down-regulate HBV replication by binding to the viral target sequence, contributing to the persistent/chronic infection of HBV, and that HBV-induced modulation of miR-122 expression may represent a mechanism to facilitate viral pathogenesis.Keywords
Funding Information
- National Basic Research Program of China (2011CB504800, 2012CB518900)
- Major State Basic Research Development Program of China (2005CB522901, 2007CB512803)
- National Natural Science Foundation of China (30730001, 81171525, 30570070, 31100128, 81030031)
- National Institutes of Health (AI041927, AI050468, DE014842)
This publication has 32 references indexed in Scilit:
- Identification of Virus-Encoded MicroRNAsScience, 2004
- Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiationGenome Biology, 2004
- Prediction of Mammalian MicroRNA TargetsCell, 2003
- Identification of Tissue-Specific MicroRNAs from MouseCurrent Biology, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- An Extensive Class of Small RNAs in Caenorhabditis elegansScience, 2001
- Identification of Novel Genes Coding for Small Expressed RNAsScience, 2001
- Global cancer statisticsCA: A Cancer Journal for Clinicians, 1999
- THE MOLECULAR BIOLOGY OF THE HEPATITIS B VIRUSESAnnual Review of Biochemistry, 1987
- Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA.Proceedings of the National Academy of Sciences of the United States of America, 1987