The role of microRNAs in viral infection.
ABSTRACT MicroRNAs (miRNAs) are small non-coding RNA molecules that have emerged in recent years as central regulators of eukaryotic gene expression. In mammalian systems, miRNAs are associated with numerous pathological and physiological pathways. miRNAs are important in many viral infections, with different viral families expressing their own miRNAs, manipulating host miRNA expression, or showing direct or indirect regulation by host or viral miRNAs. In this chapter we will examine the current evidence for interplay between the miRNA pathway and viral infections in mammals.
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ABSTRACT: Previous studies have shown that hepatitis B virus (HBV) interferes with host antiviral immunity via multiple pathways. In clinical practice, interferon resistance is a serious issue for treatment of HBV infection. Now, miRNAs have been reported to be widely involved in antiviral immunity and have become a novel tool to study virus-host interaction. We question whether miRNAs play a role in HBV-induced interferon resistance in hepatocytes. MiRNAs levels in HepG2 and HepG2.2.15 cells were compared by qRT-PCR. The effects of miR146a on HBV infection were characterized by interference miR146a level, followed by the quantification of HBV mRNA, DNA and antigens. We employed qRT-PCR and western blot to study the effects of miR146a on the IFN-α signalling pathway. The miR146a promoter activity was validated by a luciferase reporter assay. HBV infection impaired IFN-α signalling pathway in hepatocytes. MiR146a was upregulated in HBV+ HepG2.2.15 cells, and the transcriptional activity of miR146a in HepG2.2.15 cells was increased compared with HepG2 cells. HBV infection, especially the introduction of HBx, induced miR146a expression in vitro. Moreover, miR146a attenuated the production of type I interferon-induced antiviral factors. Low STAT1 levels were noticed in HBV+ HCC cells, and the luciferase reporter assay showed that STAT1 was post-transcriptionally downregulated by miR146a. Furthermore, the silencing of miR146a by antisense inhibitors enhanced IFN-α-mediated anti-HBV efficiency. Our findings demonstrate that HBV infection promotes miR146a transcription, which represses STAT1 and results in interferon resistance. These observations reveal a novel role for miR146a in HBV immunopathogenesis, and provide a potential target for the therapeutic recovery of IFN-α-induced anti-HBV effects.Liver international: official journal of the International Association for the Study of the Liver 06/2013; · 3.87 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) is a global health problem with an estimated 170-200 million peoples (approximately 3% of world population) are chronically infected worldwide and new infections are predicted to be on rise in coming years. HCV infection remains categorized as a major risk factor for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. There has been considerable improvement in our understanding of virus life cycle since, the discovery of HCV two-decades ago. MicroRNAs (miRNAs) are important players in establishment of HCV infection and their propagation in infected hepatocytes. They target crucial host cellular factors needed for productive HCV replication and augmented cell growth. Very first anti-miRNA oligonucleotides, miravirsen has been tested in clinical trial and shown promising results as therapeutic agent in treatment against chronic HCV infection. Deregulated expression of miRNAs has been linked to the pathogenesis associated with HCV infection by controlling signaling pathways such as, proliferation, apoptosis and migration. Circulating miRNAs emerging as growing field in identification of biomarkers in disease progression and their potential as a means of communication between cells inside the liver is an exciting area of research in future. This review focuses on recent studies enforcing the contribution of miRNAs in HCV life cycle and coordinated regulation in HCV mediated liver disease progression.World journal of hepatology. 09/2013; 5(9):479-486.
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ABSTRACT: In chronic liver disease leading to fibrosis, hepatic stellate cells (HSC) differentiate into myofibroblasts. Myofibroblastic HSC have taken center stage during liver fibrogenesis, due to their remarkable synthesis of extracellular matrix proteins, their secretion of profibrogenic mediators and their contribution to hypertension, due to elevated contractility. MicroRNAs (miRNAs) are small, noncoding RNA molecules of 19-24 nucleotides in length. By either RNA interference or inhibition of translational initiation and elongation, each miRNA is able to inhibit the gene expression of a wide panel of targeted transcripts. Recently, it was shown that altered miRNA patterns after chronic liver disease highly affect the progression of fibrosis by their potential to target the expression of extracellular matrix proteins and the synthesis of mediators of profibrogenic pathways. Here, we underline the role of miRNAs in the interplay of the profibrogenic cell communication pathways upon myofibroblastic differentiation of hepatic stellate cells in the chronically injured liver.International Journal of Molecular Sciences 01/2014; 15(6):9360-71. · 2.46 Impact Factor