Genetic heterogeneity of hepatitis C virus. The clinical significance of genotypes and quasispecies behavior.

Knowledge of the molecular biology of the hepatitis C virus (HCV) has increased exponentially since its identification in 1989. Paradoxically, the understanding of many clinical aspects of HCV pathobiology has lagged behind, partly because of lack of suitable models of disease. The genomic variability of HCV is central to viral pathogenesis. This article briefly reviews some clinical and laboratory aspects of HCV variability, such as investigatory method, pitfalls in data interpretation, and possible directions for future research. The profound implications of stable quasispecies behavior, conserved genotype replication, and the unexpectedly low frequency of infection with multiple genotypes in susceptible individuals are discussed.