کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8751589 | 1594203 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Establishment of robust HCV genotype 4d, 5a, and 6a replicon systems
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Hepatitis C Virus (HCV) is a diverse human pathogen which displays ~15% divergence at the subtype level. To facilitate development of antivirals with pan-genotype activity, we developed the first genotype 4d subgenomic replicon, as well as new replicons for genotypes 5a, and 6a. Adaptive mutations developed in these replicons differ greatly across genotypes. Their impacts on the replication capacity were tested using site-directed mutants. In the genotype 4d replicon, single mutations have moderate effect, but the double mutation NS4A-Q34R+NS5A-S232G increased the replication capacity by 161-fold. These new stable replicon cell lines were used to determine the antiviral activity of HCV inhibitors. The NS3 protease inhibitor voxilaprevir, NS5A second generation inhibitor velpatasvir, and NS5B nucleoside analog inhibitor sofosbuvir, had similar antiviral activities across the different genotypes/subtypes tested, while the NS5A first generation inhibitor, ledipasvir, had very good antiviral activity against GT1, 4, 5, and 6 in vitro.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 514, 15 January 2018, Pages 134-141
Journal: Virology - Volume 514, 15 January 2018, Pages 134-141
نویسندگان
Gregory Camus, Simin Xu, Bin Han, Julia Lu, Hadas Dvory-Sobol, Mei Yu, Guofeng Cheng, Michael D. Miller, Brian P. Doehle, Hongmei Mo,