The Envelope Glycoprotein of Simian Immunodeficiency Virus Contains an Enterotoxin Domain

Abstract

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.

The Virotoxin Model of HIV-1 Enteropathy: Involvement of GPR15/Bob and Galactosylceramide in the Cytopathic Effects Induced by HIV-1 gp120 in the HT-29-D4 Intestinal Cell Line

“…Based on these data and on previous reports [in particular 6,8,10,35], we propose the following hypothesis for explaining the role of gp120 in the pathogenesis of HIV-1 enteropathy.…”

“…Similar concentrations of SIV surface envelope glycoprotein (in the range of 75-300 nM) are needed to induce calcium or inositol triphosphate signals in HT-29 cells [35]. Swaggerty et al [35] observed that SIV surface envelope glycoprotein (0.02-0.45 nmol) induced a dose-dependent diarrhea in a mouse pup model.…”

“…Similar concentrations of SIV surface envelope glycoprotein (in the range of 75-300 nM) are needed to induce calcium or inositol triphosphate signals in HT-29 cells [35]. Swaggerty et al [35] observed that SIV surface envelope glycoprotein (0.02-0.45 nmol) induced a dose-dependent diarrhea in a mouse pup model. Overall, the concentrations of gp120 used in the present study are very similar to those previously used to demonstrate the enterotoxic properties of SIV surface envelope glycoprotein [35].…”

“…Swaggerty et al [35] observed that SIV surface envelope glycoprotein (0.02-0.45 nmol) induced a dose-dependent diarrhea in a mouse pup model. Overall, the concentrations of gp120 used in the present study are very similar to those previously used to demonstrate the enterotoxic properties of SIV surface envelope glycoprotein [35]. On the other hand, we observed that the sensitivity to gp120 varies markedly, depending on whether the HT-29 cells are differentiated.…”

“…The recent demonstration that the surface envelope glycoprotein of simian immunodeficiency virus (SIV) induces an experimental enteropathy in an animal model strongly supports this view [35]. Recombinant gp120 causes calcium signaling and microtubule disruption in vitro [8,10].…”