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Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent

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  1. Production and characterization of high-titer serum-free cell culture grown hepatitis C virus particles of genotype 1-6

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  2. Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

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  3. Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon

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  1. Associations between blood cultures after surgery for colorectal cancer and long-term oncological outcomes

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  2. The Glycemic Gap and 90-Day Mortality in Community-acquired Pneumonia: A Prospective Cohort Study

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  3. Prevalence and risk factors of prolonged QT interval and electrocardiographic abnormalities in persons living with HIV

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Ribavirin remains relevant for successful treatment of chronic hepatitis C virus (HCV) infections in low-income settings, as well as for therapy of difficult-to-treat HCV patients. We studied the effect of ribavirin against cell-culture adapted HCV of genotypes 1, 2 and 3, representing ~80% of global infections. TNcc(1a) was the most sensitive to ribavirin, while J6/JFH1(2a) was the most resistant. EC50s ranged from 21 μM (95%CI: 20-22 μM) to 189 μM (95%CI: 173-207 μM). Substitutions at position 415 of NS5B resulted in little or no change to ribavirin sensitivity (0.7-0.9 fold) but conferred moderate drug resistance during extended treatment of genotype 1 (1.8-fold). NS5A and NS5B sequences could alter ribavirin sensitivity 2-4-fold, although their contribution was not simply additive. Finally, we detected limited accumulation of mutations associated with ribavirin treatment. Our findings show that the antiviral effect of ribavirin on HCV is strain-dependent and is influenced by the specific sequence of multiple HCV nonstructural proteins.

Original languageEnglish
JournalVirology
Volume540
Pages (from-to)132-140
Number of pages9
ISSN0042-6822
DOIs
Publication statusPublished - 15 Jan 2020

ID: 58503035