Reclassification of the Caliciviridae into distinct genera and exclusion of hepatitis E virus from the family on the basis of comparative phylogenetic analysis

Caliciviridae and Picornaviridae belong to the same subphylum and genera within Picornaviridae are well characterized. Until 1998, Caliciviridae included one genus Calicivirus, containing strains with distinct structural and genomic features. Phylogenetic analyses of capsid genes revealed five clusters within Caliciviridae corresponding to differences in genome organization. In order to determine to what taxonomic level these clusters correspond, genomic sequences of caliciviruses, picornavirus prototypes, and two togavirus strains were analyzed. Distance and maximum likelihood methods were used to estimate the phylogenetic relationships among strains. Analysis of the capsid gene revealed separation of five main clusters (Norwalk-like, and Sapporo-like human caliciviruses, hepatitis E virus, vesicular exanthem of swine-like, and lapine caliciviruses) and distances corresponding to those observed among picornavirus genera. Utilizing more conserved (presumed helicase and polymerase) regions for the analyses, only major groups of caliciviruses were separated with confidence, with distances also comparable to those separating picornavirus genera. Analysis in these regions that included togavirus sequences moved HEV strains out of the calicivirus cluster. Our findings support the reclassification of caliciviruses into four genera. The phylogenetic position of hepatitis E virus, by analysis of non-structural genes, is outside of the caliciviruses, in an uncertain taxonomic position.