Analysis of sequential hepatitis A virus strains reveals coexistence of distinct viral subpopulations

Abstract

Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae. Despite a remarkable antigenic stability, recent results have shown that HAV exists in vivo and in cell culture as distributions of genetically related, non-identical variants, referred to as quasispecies. To gain insight into HAV evolution over time in a specific geographical region, genotype I consensus sequences from strains isolated in France in consecutive years were studied. Phylogenetic neighbour-joining method and a non-hierarchical partition analysis, designed to analyse viral quasispecies, indicate that at least five distinct subpopulations of HAV were identified in the course of the disease episode. Strikingly, over time, different subpopulations cycled in dominance. The coexistence of distinct subpopulations whose frequency varies with time is consistent with quasispecies dynamics, and suggests that variation in the dominant HAV population may provide HAV adaptability without being reflected in significant antigenic variation.