ASSESSMENT OF HEPATITIS-C VIRUS QUASI-SPECIES HETEROGENEITY BY GEL SHIFT ANALYSIS - CORRELATION WITH RESPONSE TO INTERFERON THERAPY

Hepatitis C virus (HCV) quasispecies heterogeneity was assessed in pre treatment sera of 22 patients treated with interferon (IFN). Quasispec ies heterogeneity was quantitated by analysis of 490 hypervariable reg ion 1 (HVR1) clones using gel shift analysis (GSA), which allowed dete rmination of two components of HCV quasispecies heterogeneity: genetic complexity (number of variants) and genetic diversity (mean genetic d istance between variants). HCV genotype and pretreatment RNA titer wer e similar between responders (n = 12) and nonresponders (n = 10), GSA correlated well with nucleotide sequencing for estimating HCV genetic diversity (R = .952; P < .001), A positive correlation of .666 (P < .0 01) was observed between genetic diversity and complexity, suggesting that these components of quasispecies heterogeneity were related, Howe ver, while there were no significant differences in pretreatment compl exity or genetic diversity among response groups, higher pretreatment genetic diversity was predictive of response failure (P = .041), Asses sment of HVR1 heterogeneity by GSA revealed important relationships be tween quasispecies genetic diversity, complexity, and response to IFN therapy and suggested a need for analysis of other HCV genes.