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原帖由yaoming发表于 2011-3-19 15:11
最近有一些microRNAs与HBV复制的关系陆续出来,相信目前仍然有不少人还在做这方面,以后也会陆续报道。供参考!
Nucleic Acids Res. 2011 Feb 11. [Epub ahead of print]
Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen.
Potenza N, Papa U, Mosca N, Zerbini F, Nobile V, Russo A.
Department of Life Sciences, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
Abstract
MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have shown that a limited number of mammalian microRNAs are also involved in anti-viral defense. In this study, the analysis of the hepatitis B virus (HBV) genome by the computer program MiRanda led to the identification of seven sites that are potential targets for human liver microRNAs. These sites were found to be clustered in a 995-bp segment within the viral polymerase ORF and the overlapping surface antigen ORF, and conserved among the most common HBV subtypes. The HBV genomic targets were then subjected to a validation test based on cultured hepatic cells (HepG2, HuH-7 and PLC/PRF/5) and luciferase reporter genes. In this test, one of the selected microRNAs, hsa-miR-125a-5p, was found to interact with the viral sequence and to suppress the reporter activity markedly. The microRNA was then shown to interfere with the viral translation, down-regulating the expression of the surface antigen. Overall, these results support the emerging concept that some mammalian microRNAs play a role in virus-host interaction. Furthermore, they provide the basis for the development of new strategies for anti-HBV intervention.
PMID: 21317190 [PubMed - as supplied by publisher]
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Biochem Biophys Res Commun. 2010 Aug 6;398(4):771-7. Epub 2010 Jul 13.
miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV.
Qiu L, Fan H, Jin W, Zhao B, Wang Y, Ju Y, Chen L, Chen Y, Duan Z, Meng S.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
Abstract
As the most abundant liver-specific microRNA (miRNA), miR-122 has been extensively studied for its role in the regulation of lipid metabolism, hepatocarcinogenesis and hepatitis C virus (HCV) replication, but little is known regarding its role in the replication of Hepatitis B virus (HBV), a highly prevalent hepatotropic virus that can cause life-threatening complications. In this study we examined the effects of antisense inhibition of miR-122 and transfection of a miR-122 mimic on HBV expression in hepatoma cells. The over-expression of miR-122 inhibited HBV expression, whereas the depletion of endogenous miR-122 resulted in increased production of HBV in transfected cells. We further found that the down-regulation of Heme oxygenase-1 (HO-1) by miR-122 plays a negative role in the miR-122-mediated inhibition of viral expression. Our study demonstrates the anti-HBV activity of miR-122, suggesting that therapies that increase miR-122 and HO-1 may be an effective strategy to limit HBV replication.
Copyright (c) 2010 Elsevier Inc. All rights reserved.
PMID: 20633528 [PubMed - indexed for MEDLINE]
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Virus Genes. 2010 Nov 28. [Epub ahead of print]
Targets for human encoded microRNAs in HBV genes.
Wu FL, Jin WB, Li JH, Guo AG.
College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Abstract
MicroRNAs (miRNAs) are increasingly being shown to play vital roles in development, apoptosis, and oncogenesis by interfering with gene expression at the post-transcriptional level. miRNAs, in principle, can contribute to the repertoire of host-pathogen interactions during infection by the Hepatitis B virus (HBV). Using a consensus-scoring approach, high-scoring miRNA-target pairs were selected, which were identified by four well-established target-prediction softwares. The miRNAs miR-7, miR196b, miR433, and miR511 target the polymerase or S gene of HBV, miR205 targets the X gene, and miR345 targets the preC gene. The minimum free-energy values for the bound complexes were the lowest, and the rules so far observed for miRNA-target pairing, namely, (1) pairing at a continuous stretch of 6-7 bases toward the 5'-end of the miRNA and (2) incomplete complementarity with the target sequence, were found to be valid. The target regions were highly conserved across the various clades of HBV. miRNA expression profiles from previously reported Solexa-sequencing based experiments showed that the four human miRNAs are expressed in the liver. This is the first report of human miRNAs that can target crucial HBV genes.
PMID: 21113793 [PubMed - as supplied by publisher]
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Antiviral Res. 2010 Nov;88(2):169-75. Epub 2010 Aug 20.
Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210.
Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H.
Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin 300070, China.
Abstract
Accumulating evidence suggests that microRNAs (miRNAs) control the replication of both RNA and DNA viruses. In order to determine whether host-encoded miRNAs affect hepatitis B virus (HBV) replication, antisense oligonucleotides (ASOs) of 328 identified human miRNAs were transfected into HepG2 2.2.15 cells, respectively. ELISA and MTS assay were used to measure the expression level of HBV S protein (HBsAg), HBV e antigen (HBeAg) and cell proliferation. Compared to experimental controls, miR-199a-3p and miR-210 efficiently reduced HBsAg expression without affecting HepG2 2.2.15 cell proliferation. Quantification of HBV DNA by real-time PCR showed that both miRNAs suppressed viral replication. Bioinformatics analysis indicated a putative binding site for miR-199a-3p in the HBsAg coding region and a putative binding site for miR-210 in the HBV pre-S1 region. The direct effect of miRNAs on the target region in HBV transcripts was validated by a fluorescent reporter assay, and the suppression of HBs gene expression by both miRNAs was measured by real-time PCR and Western blot. These results suggest that up-regulation of miR-199a-3p and miR-210 in HepG2 2.2.15 cells compared to HepG2 cells may play a role in regulating HBV replication and maintenance of a suitable level of virion production in persistent infection by targeting crucial HBV genes.
Copyright © 2010 Elsevier B.V. All rights reserved. |
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