Rotavirus NSP4 sub(114-135) peptide has no direct, specific effect on chloride transport in rabbit brush-border membrane

The direct effect of the rotavirus NSP4 sub(114-135 )and Norovirus NV sub(464- 483 )peptides on super(36)Cl uptake was studied by using villus cell brush border membrane (BBM) isolated from young rabbits. Both peptides inhibited the Cl super(- )/H super(+ )symport activity about equally and partially. The interaction involved one peptide-binding site per carrier unit. Whereas in vitro NSP4 sub(114-135 )caused nonspecific inhibition of the Cl super(-)/H super(+ )symporter, the situation in vivo is different. Because rotavirus infection in young rabbits accelerated both Cl super(- )influx and Cl super(- )efflux rates across villi BBM without stimulating Cl super(- )transport in crypt BBM, we conclude that the NSP4 sub(114-135 )peptide, which causes diarrhea in young rodents, did not have any direct, specific effect on either intestinal absorption or secretion of chloride. The lack of direct effect of NSP4 on chloride transport strengthens the hypothesis that NSP4 would trigger signal transduction pathways to enhance net chloride secretion at the onset of rotavirus diarrhea.