The envelope glycoprotein of simian immunodeficiency virus contains an enterotoxin domain

By the use of a mouse model, the enteropathic effects of the simian immunod eficiency virus (SIV) surface unit (SU) envelope glycoprotein were explored . Purified SU (0.01-0.45 nmol) was administered intraperitoneally to 6- to 8-day-old mouse pups and induced a dose-dependent diarrhea[ response. Surgi cal introduction of SU into adult mouse intestinal loops revealed fluid acc umulation without histological alterations and SU-treated unstripped intest inal mucosa induced chloride (Cl-) secretory currents in Ussing chambers. S imilarly to rotavirus NSP4 the first described viral enterotoxin, SU induce d a transient increase in intracellular calcium levels and increased inosit ol 1,4,5-triphosphate (IP3) levels in HT-29 cells. These data indicate the calcium response is mediated by IP3. The presence of diarrhea and fluid acc umulation within intestinal loops in the absence of histological alteration s and induction of Cl- secretory currents demonstrate that SIV contains an enterotoxic domain localized within SU and is the second viral enterotoxin described, (C) 2000 Academic Press.