Diarrhea induction by rotavirus NSP4 in the homologous mouse model system

Comparison of the NSP4 amino acid sequences from 31 strains of mammalian ro taviruses revealed the presence of four distinct NSP4 alleles; i.e., the Wa , KUN, AU-1, and EW alleles. The EW allele consists only of NSP4s from muri ne rotavirus strains and is divergent from other NSP4 alleles from the evol utionary perspective. There have been conflicting reports regarding the ent erotoxigenic activity of NSP4 in the mouse model system; heterologous simia n and porcine rotavirus NSP4s function as an enterqtoxin in mice, while a h omologous EC NSP4 does not play a dominant role as an enterotoxin in the cy stic fibrosis conductance regulator knockout mice. To further examine the e nterotoxigenic activity of NSP4, we expressed in Escherichia coli a recombi nant protein consisting of glutathione S-transferase and amino acid residue s 86-175 of the EW NSP4. We found that this fusion protein caused diarrhea in the majority (8/14) of 5- to 6-day-old CD1 mice. This study confirmed an d extended that group A rotavirus NSP4s were able to induce diarrhea in neo natal mice and had an enterotoxigenic activity. (C) 1999 Academic Press.