Enterotoxigenic activity of rotavirus NSP4

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Rotaviruses are established as an important cause of severe diarrhea in young animals as well as infants and young children. The rotavirus genome consists of 11 segments of double-stranded RNA that are contained within a triple-layered capsid. Gene segment 10 encodes nonstructural protein 4 (NSP4) which plays an important role in rotavirus morphogenesis. The NSP4 protein has captured much greater attention since it was eported for the first time that SA11 NSP4 has an enterotoxigenic activity in suckling mice. However, controversy continues to date whether its real role in diarrheal pathogenesis. The phylogenetic analysis for 31 NSP4s from the group A rotavirus strains allowed identification of the four distinct NSP4 alleles ; the Wa, KUN, AU-1, and EW alleles, meaning that murine NSP4s are genetically different from other mammalian rotavirus NSP4s. By contrast, the basic structure of the group A rotavirus NSP4 protein was well conserved judging from the almost identical hydrophobic profiles according to the Kyte and Doolittle algorithm. We speculate that the enterotoxigenic activity of the NSP4 protein is dependent on the consistent structural features and the well conserved putative receptor binding site at residues 114-130. We conclude that group A rotavirus NSP4 has an eterotoxigenic activity when given intraperitoneally into neonatal mice. We also speculate that the NSP4 protein plays an important role in inducing diarrhea at the early stage of infection.