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

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Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent. / Mejer, Niels; Galli, Andrea; Ramirez, Santseharay; Fahnøe, Ulrik; Benfield, Thomas; Bukh, Jens.

In: Virology, Vol. 540, 2020, p. 132-140.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mejer, N, Galli, A, Ramirez, S, Fahnøe, U, Benfield, T & Bukh, J 2020, 'Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent', Virology, vol. 540, pp. 132-140. https://doi.org/10.1016/j.virol.2019.09.014

APA

Mejer, N., Galli, A., Ramirez, S., Fahnøe, U., Benfield, T., & Bukh, J. (2020). Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent. Virology, 540, 132-140. https://doi.org/10.1016/j.virol.2019.09.014

Vancouver

Mejer N, Galli A, Ramirez S, Fahnøe U, Benfield T, Bukh J. Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent. Virology. 2020;540:132-140. https://doi.org/10.1016/j.virol.2019.09.014

Author

Mejer, Niels ; Galli, Andrea ; Ramirez, Santseharay ; Fahnøe, Ulrik ; Benfield, Thomas ; Bukh, Jens. / Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent. In: Virology. 2020 ; Vol. 540. pp. 132-140.

Bibtex

@article{bf710b4dd7da4d1d91a8d43bec1fa462,
title = "Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent",
abstract = "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.",
keywords = "Antivirals, Cell culture, Genotype, HCV, Hepatitis C virus, In vitro, Mechanism, Polymerase, Ribavirin",
author = "Niels Mejer and Andrea Galli and Santseharay Ramirez and Ulrik Fahn{\o}e and Thomas Benfield and Jens Bukh",
year = "2020",
doi = "10.1016/j.virol.2019.09.014",
language = "English",
volume = "540",
pages = "132--140",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent

AU - Mejer, Niels

AU - Galli, Andrea

AU - Ramirez, Santseharay

AU - Fahnøe, Ulrik

AU - Benfield, Thomas

AU - Bukh, Jens

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Antivirals

KW - Cell culture

KW - Genotype

KW - HCV

KW - Hepatitis C virus

KW - In vitro

KW - Mechanism

KW - Polymerase

KW - Ribavirin

U2 - 10.1016/j.virol.2019.09.014

DO - 10.1016/j.virol.2019.09.014

M3 - Journal article

C2 - 31778898

AN - SCOPUS:85075387173

VL - 540

SP - 132

EP - 140

JO - Virology

JF - Virology

SN - 0042-6822

ER -

ID: 235589980