کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5822299 | 1557843 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of proteins that mediate the pro-viral functions of the interferon stimulated gene 15 in hepatitis C virus replication
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کلمات کلیدی
non-parenchymal liver cellsubiquitin specific peptidase 18hydroxymethylglutaryl-CoA synthaseHeterogeneous nuclear ribonucleoprotein KRibonuclease LMx2RNASELPSMA6hnRNPKHERC5HMGCS1LNPRSAD2IFITM3IDH1ACADMISG15USP18PMHNPCPolyI:C - PolyI: CSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAinterferon - اینترفرونIFN - اینترفرون هاLipid nanoparticles - نانوذرات لیپیدیHepatitis C virus - هپاتیت سیHCV - هپاتیت سیPolyinosinic:polycytidylic acid - پلی سونیک: پلیسییدیدیل اسید
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
In previous studies we identified the interferon stimulated gene 15 (ISG15) as a pro-viral host factor in the pathogenesis of hepatitis C virus (HCV) infection. However, the functional link between ISG15 and the HCV replication cycle is not well understood. Aim of the present study was to functionally analyze the role of ISG15 and to identify possible HCV promoting effector molecules. Isg15 suppression was investigated in the murine subgenomic HCV replicon (MH1) transfected with Isg15-specific siRNA and in C57BL/6 mice intravenously injected with lipid nanoparticles (LNP)-formulated siRNA. Interestingly, the LNP-formulated siRNA led to hepatocyte-specific knockdown of Isg15 in vivo, which mediated a hypo-responsiveness to endogenous and exogenous interferon. A label free proteome analysis accompanied by western blot and quantitative RT-PCR techniques led to identification of five candidate proteins (Heterogeneous nuclear ribonucleoprotein A3 (HnrnpA3), Heterogeneous nuclear ribonucleoprotein K (HnrnpK), Hydroxymethylglutaryl-CoA synthase (Hmgcs1), Isocitrate dehydrogenase cytoplasmic (Idh1) and Thioredoxin domain-containing protein 5 (Txndc5)) that are either involved in lipid metabolism or belong to the family of Heterogeneous nuclear ribonucleoprotein (Hnrnp). All candidate proteins are likely to be associated with the HCV replication complex. Furthermore treatment with HnrnpK-specific siRNA directly suppressed HCV replication in vitro. Taken together these data suggest that targeting Isg15 may represent an attractive novel therapeutic option for the treatment of chronic HCV infection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 100, Issue 3, December 2013, Pages 654-661
Journal: Antiviral Research - Volume 100, Issue 3, December 2013, Pages 654-661
نویسندگان
Catherine I. Real, Dominik A. Megger, Barbara Sitek, Kerstin Jahn-Hofmann, Ludger M. Ickenstein, Matthias J. John, Andreas Walker, Joerg Timm, Katja Kuhlmann, Martin Eisenacher, Helmut E. Meyer, Guido Gerken, Ruth Broering, Joerg F. Schlaak,