Characterization and genetic variability of Hepatitis A virus genotype IIIA.

Molecular epidemiological studies of hepatitis A outbreaks in Norway showed the emergence of Hepatitis A virus (HAV) genotype IIIA in association with parenteral transmission among haemophiliacs and intravenous drug users. The complete genomic sequence of one of these outbreak isolates, NOR-21, was determined. This is the first complete genomic sequence of HAV genotype IIIA. Phylogenetic analysis showed that genotype IIIA/NOR-21 was genetically distinct from the other human and simian genotypes. Phylogenetic analysis of the nucleotide sequences clearly distinguished the different HAV genotypes, regardless of the genomic region used for analysis, whereas the amino acid sequences showed a more vague distinction between human HAV genotypes I and II. In particular, the inferred phylogeny based on the capsid proteins showed that the human HAV strains were related more closely to each other than to the simian strains. The greatest variability and clearest distinction between genotypes were observed for the polymerase gene. The outbreak isolates of HAV genotype IIIA in this study showed greater nucleotide variability than is generally seen in outbreaks of genotype I. This high nucleotide variability, which may be characteristic of this HAV genotype, the mode of transmission in this outbreak or parallel introductions, is discussed.