ABSTRACT
Acute infection with hepatitis C virus is generally asymptomatic. Most patients can not clear the virus and are easy to develop into chronic infection, while a small number of patients even develop into cirrhosis, or liver cancer. The traditional treatment is combined pegylated interferon with ribavirin, but the antiviral effect is poor and the adverse reactions are large, which may be related to the ability of HCV to escape the host′s immune response through various mechanisms. The innate immune response is the first line of defense against pathogenic microorganisms. Retinoic acid inducible geneⅠ(RIG-Ⅰ) plays an important role in identifying HCV virus and initiating immune response as a pattern recognition receptor.
ABSTRACT
Objective To detect the expression of retinoic acid-inducible gene Ⅰ ( RIG-Ⅰ) in peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis C (CHC), and to explore its correlations with type Ⅰinterferon gene expression and serum level of hepatitis C virus .Methods A total of 101 na?ve patients with CHC were enrolled from Renmin Hospital of Wuhan University during July 2014 and July 2015, and 69 healthy subjects served as controls .The expressions of RIG-Ⅰ, IFNαand IFNβmRNA in PBMCs and serum level of HCV RNA were detected by real-time quantitative polymerase chain reaction.Pearson correlation analysis was performed to investigate the correlations of RIG-Ⅰ mRNA expression with IFNα/βmRNA expression and serum level of HCV RNA .Results The relative expressions of RIG-Ⅰ, IFNα, IFNβmRNA to healthy controls in CHC group were 0.082, 0.022 and 0.156, respectively (t=7.83, 3.65 and 2.13, all P0.05).Conclusion Expression of RIG-ⅠmRNA decreases in patients with CHC , and is positively correlated with that of IFNαand IFNβmRNA.
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Objective To explore the biological functions of retinoic acid-inducible gene-I(RIG-I) in vivo through phenotype analysis of RIG-I knockout mice. Methods The gene expression of RIG-Ⅰ in various tissues of mice was examined with Northern blotting and semi-quantitative RT-PCR.The phenotypes observed included body weight measurement,differential count of peripheral blood cells,metabolic parameters measurement and histopathologic examination. ResultsRIG-Ⅰ expressed in various tissues of mice with different levels.No gross developmental abnormalities and expected maturation arrest in granulocytic differentiation were observed in RIG-Ⅰ knockout mice.However,RIG-Ⅰ knockout mice exhibited an unexpected increase in the ratios of neutrophiles to lymphocytes in peripheral blood and increased susceptibility to bacteria infection. Conclusion RIG-Ⅰ may play an important role in immune regulation in mice.
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Objective To study the regulatory effect of interferons(IFNs) on retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ) and the roles of RIG-Ⅰ in IFNs signaling pathway. Methods RIG-Ⅰ expression before and after IFNs treatment in mouse embryonic fibroblasts(MEFs) were analyzed with Northern blotting and semi-quantitative RT-PCR assay.MEFs isolated from wild-type and RIG-Ⅰ-/-mice were used to test growth inhibition and antiviral activity of IFNs with MTT assay and cytopathic effect inhibition assay. Results Both IFN-? and IFN-? could induce RIG-Ⅰ expression in MEFs.Treated with 100 U/mL IFN-?,growth inhibition and antiviral activity of MEFs from wild-type mice were more significant than those from RIG-Ⅰ-/-mice.With the absence of RIG-Ⅰ,the antiviral protective role IFN-? plays was significantly weaker than the wild type. Conclusion RIG-Ⅰ gene is a novel mediator of interferon effects on cells.It may participate in the inflammation responses mediated by IFNs through modulating cytokines production.
ABSTRACT
RIG-Ⅰ, the abbreviation of retinoic acid inducible gene-Ⅰ, can be induced to express in many type cells by various stimuli. Recently, it was identified as an intracellular regulator for RNA virus-induced antiviral response in innate immunity. Its discovery, expression induction, structure, research status of its function, homologous proteins and functional mechanism etc. were summarized, and its further research pulses are also prospected meanwhile.