Recombination in hepatitis A virus: evidence for reproductive isolation of genotypes

This study analysed phylogenetic evidence of recombination in sequences of hepatitis A virus (HAV) available in international databases. Isolation of distinct recombinant HAV strains has been reported previously; however, the prevalence of natural recombination and its role in HAV genetics remains obscure. Analysis of full genome sequences revealed evidence of common intratypic recombination among the most prevalent subtypes, IA and IIIA. Many of the available complete sequences of these genotypes carried phylogenetic signs of recombination in all genomic regions without obvious hotspots. In addition, and in line with previous reports, recombination between subtypes IA and IB was detected. A dataset of 104 published HAV sequences for the VP1-2A and 3CD genomic regions was also analysed. Multiple instances of phylogenetic incompatibility were found among subtypes IA and IIIA. Three cases of recombination disrupted the phylogenetic grouping of subtype IA HAV strains isolated in Japan within less than 4 years, indicating common intratypic recombination in HAV. There were no signs of recombination between different HAV genotypes, despite the fact that co-circulation of genotypes IA and IIIA has commonly been reported in different parts of the world and many sequences in the sampling in this study originated from the same geographical region. These results indicate that there is reproductive isolation between genotypes of HAV, as exists between enterovirus species, and suggest that common intratypic recombination constrains the diversity within a genotype and maintains HAV genotypes as global gene pools.