Three major alleles of rotavirus NSP4 proteins identified by sequence analysis.

Comparison of nonstructural glycoprotein NSP4 gene sequences from 22 rotavirus strains originating from six host species and of 14 different combinations of G and P types revealed the presence of three distinct NSP4 alleles, represented by strains Wa, KUN and AU-1. Genetic distances between any of these alleles (18.0%) were significantly greater than those within each allele (5.5%) and phylogenetic analysis suggested that divergence into three distinct alleles had occurred at about the same time during evolution. While amino acid variation among strains was minimal in the amino-terminal two-thirds of the protein (aa 1-130), variability increased toward the carboxy terminus of the enterotoxic peptide region (aa 114-135) and was greatest between residues 135 and 141. Comparison of the amino acid sequences corresponding to the enterotoxic peptide region between strains isolated from asymptomatic neonates and those from children with diarrhoea failed to identify any conserved changes that correlated with the capacity of the virus to cause disease. Amino acids were relatively conserved in the domains important for viral morphogenesis.