Classification, Genetic Diversity and Global Distribution of Hepatitis C Virus (HCV) Genotypes and Subtypes

Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus that belongs to the family Flaviviridae. HCV is characterized by extensive genetic heterogeneity and has been classified into genotypes, subtypes and recombinant forms (RFs). Revised HCV classification, based on phylogenetic analysis of a large number of nearly full-length sequences, has revealed the existence of seven major clades named genotypes 1–7. These genotypes have been further divided into 86 subtypes. Τhe distribution of genotypes, subtypes and RFs differs greatly with the geographic origin. Subtypes 1a, 1b, 2a and 3a are the most widely spread, being highly prevalent in high-income countries. They are known as the “epidemic subtypes”, and they have spread mostly as a result of blood and blood product transfusions, iatrogenic procedures and injecting drug use. Their global dissemination occurred before the identification of HCV in 1989. The remaining HCV subtypes are mostly prevalent in restricted geographic areas, and they are characterized as “endemic”. The genetic diversity of HCV is higher than that of the human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV), because HCV has been infecting humans for a longer time period compared to HIV-1 and does not have the overlapping reading frames present in HBV, which constrain the molecular evolution of HBV. HIV-1 group M is the result of a cross-species transmission event from chimpanzee that occurred approximately at the beginning of the twentieth century, suggesting a recent origin in humans. HBV, on the other hand, has co-expanded with modern humans for approximately 34,100 years, coinciding with the dispersal of modern non-African humans. Although HBV has been infecting humans for several 1000 years, the presence of overlapping reading frames in the viral genome decelerates its evolutionary rate making HBV less divergent than HCV.