The Envelope Glycoprotein of Simian Immunodeficiency Virus Contains an Enterotoxin Domain

By the use of a mouse model, the enteropathic effects of the simian immunodeficiency 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 diarrheal response. Surgical introduction of SU into adult mouse intestinal loops revealed fluid accumulation without histological alterations and SU-treated unstripped intestinal mucosa induced chloride (Cl − ) secretory currents in Ussing chambers. Similarly to rotavirus NSP4, the first described viral enterotoxin, SU induced a transient increase in intracellular calcium levels and increased inositol 1,4,5-triphosphate (IP 3 ) levels in HT-29 cells. These data indicate the calcium response is mediated by IP 3 . The presence of diarrhea and fluid accumulation within intestinal loops in the absence of histological alterations and induction of Cl − secretory currents demonstrate that SIV contains an enterotoxic domain localized within SU and is the second viral enterotoxin described.