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Volume 132, Issue 3, Pages (March 2007)

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Presentation on theme: "Volume 132, Issue 3, Pages (March 2007)"— Presentation transcript:

1 Volume 132, Issue 3, Pages 921-930 (March 2007)
Mutagenic Effect of Ribavirin on Hepatitis C Nonstructural 5B Quasispecies In Vitro and During Antiviral Therapy  Wolf Peter Hofmann, Andreas Polta, Eva Herrmann, Ulrike Mihm, Bernd Kronenberger, Tanja Sonntag, Volker Lohmann, Barbara Schönberger, Stefan Zeuzem, Christoph Sarrazin  Gastroenterology  Volume 132, Issue 3, Pages (March 2007) DOI: /j.gastro Copyright © 2007 AGA Institute Terms and Conditions

2 Figure 1 NS5B mutational frequencies in ribavirin- or levovirin-treated HCV replicon cells. Huh7 cells harboring subgenomic HCV replicon cells were treated with different concentrations of ribavirin or levovirin for 24, 48, or 72 hours, respectively. The NS5B mutational frequency (mean) is calculated as the number of mutations/clones/nucleotides sequenced in comparison with the consensus sequence of each NS5B population (see also Table 2). A mean number of 17 clones per sample were sequenced. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2007 AGA Institute Terms and Conditions

3 Figure 2 Nucleotide mutational frequencies of NS5B quasispecies in patients with chronic hepatitis C. The total mutational frequency is calculated as the number of mutations/clones/nucleotides sequenced in comparison with the consensus sequence of each individual quasispecies population. Shown is the mutational frequency and mean of all HCV quasispecies sequenced prior treatment in comparison with (A) all sequences at baseline, (B) all sequences at baseline and during ribavirin monotherapy, and (C) during pegylated IFN-α/ribavirin combination therapy. Each data point represents a single NS5B quasispecies sequence (for details, see text). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2007 AGA Institute Terms and Conditions

4 Figure 3 Individual mutational frequencies of HCV quasispecies at baseline and during antiviral therapy. (A) Mutational frequencies of all NS5B and NS3 quasispecies sequenced at baseline and during therapy (days) in individual patients receiving ribavirin monotherapy and (B) mutational frequencies of all NS5B quasispecies sequenced in individual patients receiving pegylated IFN-α/ribavirin combination therapy, all sorted by increasing ribavirin serum concentrations (mg/L). A mean number of 20 and 18 clones of NS3 and NS5B quasispecies per sample and time point were sequenced. Each data point of the aligned dot plot represents a single or a group of quasispecies sequences. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2007 AGA Institute Terms and Conditions

5 Figure 4 Proportion of transition mutations in patients with chronic hepatitis C. Transitions accounted for the majority of mutations. Transitions at baseline and during (A) ribavirin monotherapy and (B) pegylated IFN-α/ribavirin combination therapy. *P < .01. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2007 AGA Institute Terms and Conditions

6 Figure 5 Association of ribavirin concentration and NS3/NS5B quasispecies heterogeneity during ribavirin monotherapy. Ribavirin serum concentration (mg/L) was measured from the same serum samples of which NS3 and NS5B quasispecies analyses were performed. The correlation (bivariate Pearson correlation coefficient) of ribavirin concentration with (A) fold increase in nucleotide mutational frequencies and (B) fold increase in amino acid mutational frequencies is shown. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2007 AGA Institute Terms and Conditions


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