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.
Swaggerty
C L
CL
Department of Pathobiology, Texas A&M University, College Station, Texas 77843-4467, USA.
Frolov
A A
AA
McArthur
M J
MJ
Cox
V W
VW
Tong
S
S
Compans
R W
RW
Ball
J M
JM
D000818:Animals; D000833:Animals, Suckling; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000633:toxicity*; D006023:Glycoproteins / Q000302:isolation & purification / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000302:isolation & purification / Q000633:toxicity*
D002712:Chlorides; D004768:Enterotoxins; D006023:Glycoproteins; D014759:Viral Envelope Proteins; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium