| 摘要 |
The invention includes methods of identifying compounds that increase the mutation rate of hepatitis C virus. The invention can be used to screen libraries of test compounds, including both nucleoside analogs and non-nucleoside analogs. The methods include: 1) contacting a test cell with a candidate compound, wherein the test cell contains a nucleic acid molecule comprising an infectious hepatitis C viral genome, a ribozyme, and an inducible promoter operably linked to the first and second nucleotide sequences, the ribozyme being configured to remove a 3' sequence unnecessary for replication of the infectious hepatitis C viral genome from a transcript initiated by the inducible promote; and 2) the detection of an increase in hepatitis C virus quasispecies produced by the cell in the presence of the candidate compound. Detection of an increase in quasispecies can be accomplished by, e.g., sequencing HCV nucleic acid molecules isolated from the test cell.
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