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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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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.

OriginalsprogEngelsk
TidsskriftVirology
Vol/bind540
Sider (fra-til)132-140
Antal sider9
ISSN0042-6822
DOI
StatusUdgivet - 15 jan. 2020

Bibliografisk note

Copyright © 2019. Published by Elsevier Inc.

ID: 58503035