Identification of eterotoxin molecules in rotavirus NSP-4 and the application for the protection of diarrhea

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The aim of this study was to determine the enterotoxin molecules in non-structural protein(NSP4) of rotaviruses which are known to be the main cause of serious diarrheal disease in infants and young mammalian animals, and to demonstrate the mechanisms underlying induction of diarrhea. In this study, group A avian rotaviruses were used. The results run as follows :1) An avian rotavirus, PO-13 strain was found to be infectious and have a similar level of virulence to that of the monkey rotavirus SA-11 in a heterologous suckling mouse model, but a turkey rotavirus, Ty-3, did not. (Virology, 2001)2)In spite of the induction of the diarrhea by virus, avian rotavirus NSP4s expressed in Escherichia coil acted as enterotoxins in suckling mice as did mammalian rotavirus NSP4s, despite great differences in the amino acid sequences. The enterotoxin molecules of PO-13 NSP4 existed in amino acid residues 109 to 135, a region similar to that reported in SA11 NSP4. (J.Virol., 2002)3)The homologies of the enterotoxin domains in NSP4s (50-59%) are higher than those (31-37%) of full-length NSP4s among the compared avian and mammalian rotaviruses. (Virus Res., 2002)4)It has demonstrated that the difference between degrees of virulence of rotaviruses for suckling mice is dependent on their outer capsid proteins, VP7 and VP4 by kinetics of reassortant strains in intestines of suckling mice. (Virology, 2003)5)From antigenic analysis of avian rotavirus NSP4 by monoclonal antibodies, it was showed that there are at least four major antigenic sites on the protein and that one of antigenic sites is widely conserved among a variety of rotaviruses. (Microbiol.Immunol., 2003)