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Published on: March 8, 2012
The envelope glycoprotein of simian immunodeficiency virus contains an enterotoxin domain
C L Swaggerty1, A A Frolov, M J McArthur
1Department of Pathobiology, Texas A&M University, College Station, Texas 77843-4467, USA.
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.
Insights
The simian immunodeficiency virus (SIV) surface unit (SU) acts as a viral enterotoxin, causing diarrhea and fluid accumulation in mice. This discovery identifies a second viral enterotoxin, highlighting SIV
Area of Science:
- Virology
- Gastroenterology
- Immunology
Background:
- The simian immunodeficiency virus (SIV) is a pathogen with complex effects.
- Viral enterotoxins contribute to gastrointestinal pathology in various infections.
- The specific enteropathic mechanisms of SIV components remain incompletely understood.
Purpose of the Study:
- To investigate the enteropathic potential of the SIV surface unit (SU) envelope glycoprotein.
- To determine if SIV SU possesses enterotoxin-like activity.
- To elucidate the cellular mechanisms underlying SIV SU-induced intestinal dysfunction.
Main Methods:
- Administration of purified SIV SU to a mouse model (pups and adult intestinal loops).
- Assessment of diarrheal response, fluid accumulation, and histological alterations.
- Ussing chamber experiments to measure chloride secretion in intestinal mucosa.
- Intracellular calcium and inositol 1,4,5-triphosphate (IP(3)) level measurements in HT-29 cells.
Main Results:
- Intraperitoneal administration of SIV SU induced a dose-dependent diarrheal response in mouse pups.
- Intestinal loops treated with SU showed fluid accumulation but no histological damage.
- SU-treated intestinal mucosa exhibited induced chloride secretory currents.
- SIV SU triggered a transient increase in intracellular calcium and IP(3) levels in HT-29 cells, indicating IP(3)-mediated calcium signaling.
Conclusions:
- The SIV surface unit (SU) contains an enterotoxic domain.
- SIV SU functions as a viral enterotoxin, causing diarrhea and fluid accumulation without overt tissue damage.
- This finding identifies SIV SU as the second described viral enterotoxin, with implications for understanding SIV pathogenesis.
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