Journal: Antimicrobial Agents and Chemotherapy

Article Title: In Vitro Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor TMC435 ▿ †

doi: 10.1128/AAC.01452-09

Figure Lengend Snippet: Summary of results from in vitro selection experiments. (A) Frequency of changes in the protease domain of NS3 (amino acids 1 to 181) observed in experiments conducted with different replicon-containing cell lines in the presence or the absence of TMC435. NS3 sequences from 120 control replicon colonies or cell pools (21 of genotype 1a and 99 of genotype 1b) and 109 TMC435-treated replicon colonies or cell pools (46 of genotype 1a and 63 of genotype 1b) were assessed. Positions at which mutations were present in more than three sequences are shown. Dark gray bars, TMC435-treated cells; white bars, control cells. (B) Frequency of mutations at one or more of NS3 positions 43, 80, 155, 156, and 168 in cells selected with TMC435. Experiments were performed with genotype 1a (Huh7-SG1a H77) or genotype 1b (Huh7-Luc and Huh7-con1b) replicon-containing cells. Mutations containing a mixture of the wild-type residue with a mutated residue are counted as containing the mutated residue only. The frequency was calculated for each subtype. Black bars, genotype 1a; light gray bars, genotype 1b.

Article Snippet: Huh7-con1b cells (i.e., a genotype 1b [con1-based] subgenomic replicon clone with cell culture-adaptive mutation S2204I in NS5A) and Huh7-SG1a H77 cells (i.e., a genotype 1a [H77-based] subgenomic replicon clone with cell culture-adaptive mutations P1496L and S2204I in NS3 and NS5A) were obtained from Apath LLC (Brooklyn, NY) ( 1 , 2 ).

Techniques: In Vitro, Selection, Control, Residue