Phylogenetic and clinical implications of recently characterized human and animal caliciviruses

Background Human caliciviruses (HuCVs) are one of four proven viral causes of diarrhea among children and adults. Animal caliciviruses (AnCVs) cause a variety of syndromes in different species including pneumonia, mucosal ulcers, spontaneous abortions, and failure to thrive. Aim To establish phylogenetic relationships among HuCVs and AnCVs at the genomic level. Methods Published HuCV and AnCV nucleotide sequences and unpublished sequences characterized in our laboratories (5 pediatric diarrhea strains, primate, dolphin, rattlesnake, sea lion, mussel, fur seal) or elsewhere (3 HuCV sequences from Dr. Lambden in Southampton) were subjected to phylogenetic analyses. Nucteotide and predicted protein sequences from a region relatively conserved among CVs (3D region, ∼450m) and a hypervariable region in the capsid gene (∼1200m) were analyzed using PHYLIP 3.5c, utilizing distance, maximum likelihood, and parsimony methods. Results Each phylogenetic method provided a similar tree topology but different levels of confidence. HuCVs and AnCVs separated into five distinct genogroups: Norwalk-like (including Norwalk and Snow Mountain viruses), Sapporo-like, and hepatitis E (HEV)-Hke HuCVs, and rabbit and feline CV like AnCVs. Each genogroup has a distinct genome organization of protein encoding regions. Each genogroup subdivides further into subgenogroups. The Sapporo-like HuCVs that include strains exclusively isolated from children are closest to the AnCVs at the nucleotide level. Conclusions This phylogenetic analysis of the Caliciviridae permits formation of the following hypotheses: 1) Animal-human transmission of CVs naturally occurs and strains in the Sapporo-like genogroup most likely are involved in cross-species transmission. 2) Viruses currently called CVs include five potential emerging virus subfamilies. 3) Extra-intestinal manifestations of HuCV infection other than hepatitis are likely. The potential for human illness in this family can be explored on the basts of this new phylogenetic information.