کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8523176 | 1557789 | 2018 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sofosbuvir inhibits hepatitis A virus replication in vitro assessed by a cell-based fluorescent reporter system
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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 A virus (HAV) infection remains a major cause of acute hepatitis worldwide and even leads to fulminant hepatitis. For screening antivirals against HAV in vitro, we develop a cell-based fluorescent reporter system named Huh-7.5.1-GA, in which HAV infection is visualized by green fluorescence protein (GFP) translocation from the cytosol into the nucleus. The reliability of Huh-7.5.1-GA for antiviral studies is validated by IFN-α, a known inhibitor of HAV replication, which impedes GFP translocation. Utilizing this in-vitro reporter system, we find that sofosbuvir, an FDA approved prodrug for the treatment of chronic hepatitis C, disturbs GFP translocation and inhibits HAV replication efficiently. In addition, we find that inhibition of HAV by sofosbuvir is hepatic-cell dependent, with IC50 (half-maximal inhibitory concentration) being 6.3â¯Î¼M and 9.9â¯Î¼M in Huh-7.5.1, quantified separately by RT-qPCR and image-based analysis. Therefore, our reporter system may serve as a high-throughput platform for screening potent antivirals against HAV. Sofosbuvir may be considered for treatment of hepatitis A, especially in re-infected patients who undergo liver transplantation due to HAV-induced liver failure.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 154, June 2018, Pages 51-57
Journal: Antiviral Research - Volume 154, June 2018, Pages 51-57
نویسندگان
Wang Jiang, Fawad Muhammad, Pengjuan Ma, Xiyu Liu, Gang Long,