Hepatitis c virus variants

Abstract

The present invention relates to HCV variants, particularly variants that are resistant to a protease inhibitors such as VX-950. Also provided are methods and compositions related to the HCV variants. Further provided are methods of isolating, identifying, and characterizing multiple viral variants from a patient.

1 - 23 . (canceled) 
     
     
         24 . A method for identifying a candidate compound for treating an HCV infection in a patient comprising:
 a) providing a sample infected with an HCV variant;   b) assaying the ability of the candidate compound in inhibiting an activity of the HCV variant in the sample;   wherein the HCV variant comprises a polynucleotide encoding an HCV NS3 protease, wherein at least one codon of the polynucleotide that corresponds to a codon selected from the group consisting of: codons 36, 41, 43, 54, 148, 155, and 156 of a wild-type HCV polynucleotide is mutated such that it encodes an amino acid different from the amino acid encoded by the corresponding codon of the wild-type HCV polynucleotide.   
     
     
         25 . The method of  claim 24 , wherein the activity of the HCV variant is replication. 
     
     
         26 . A method for identifying a candidate compound for treating or preventing an HCV infection in a patient comprising:
 a) providing a replicon RNA comprising an HCV polynucleotide;   b) determining whether the candidate compound inhibits replication of the replicon RNA of a);   wherein the HCV polynucleotide encodes an HCV NS3 protease, a biologically active analog thereof, or a biologically active fragment thereof, wherein at least one codon that corresponds to a codon selected from the group consisting of: codons 36, 41, 43, 54, 148, 155, and 156 of a wild-type HCV polynucleotide is mutated such that it encodes an amino acid different from the amino acid encoded by the corresponding codon of the wild-type HCV polynucleotide.   
     
     
         27 . (canceled) 
     
     
         28 . A method for evaluating a candidate compound for treating an HCV infection in a patient comprising:
 a) introducing a vector comprising an HCV polynucleotide and an indicator gene encoding an indicator into a host cell;   b) culturing the host cell; and   c) measuring the indicator in the presence of the candidate compound and in the absence of the candidate compound;   
       wherein the HCV polynucleotide encodes an HCV NS3 protease, a biologically active analog thereof, or a biologically active fragment thereof, wherein at least one codon that corresponds to a codon selected from the group consisting of: codons 36, 41, 43, 54, 148, 155, and 156 of a wild-type HCV polynucleotide is mutated such that it encodes an amino acid different from the amino acid encoded by the corresponding codon of the wild-type HCV polynucleotide. 
     
     
         29 - 51 . (canceled)