Genetic variation and recombination in Aichi virus.

Aichi virus (AiV), a member of the genus Kobuvirus in the family Picornaviridae, causes gastroenteritis in humans. It was noted that AiV differs from other picornaviruses in its unusually high C content and a very high degree of genome-ordered RNA secondary structures. However, the genetic variability and mutational restrictions on a full-genome scale have not been studied. In addition to the available five complete AiV genomes, we determined here another five complete coding sequences of AiV sampled in Germany, 2004. Distinctive AiV genetic features included a low incidence of recombination along the genome without obvious hotspots or spared regions and very low rates of synonymous and non-synonymous variation, supporting an absence of AiV serotypes. In addition, the absence of recombination between AiV genotypes A and B suggested the existence of reproductive isolation between taxonomic units below the species level. In contrast to most other picornaviruses, AiV genomes strongly avoided the UpA dinucleotide, while there was no obvious selection against the CpG dinucleotide. AiV genomes also appeared to contain a codon usage bias (CUB) apparent as an effective number of codons of 39.5, which was amongst the most extreme among RNA viruses. A set of sequence scrambling algorithms was developed to determine the origin of CUB in AiV. While in most picornaviruses the genomic dinucleotide content contributed significantly to CUB, in AiV its extreme nucleotide content, i.e. 57 % third codon position C, was the main driving force behind the apparent CUB.