Gp120-induced Bob/GPR15 activation: A possible cause of human immunodeficiency virus enteropathy

Frederic Clayton, Donald P. Kotler, Scott K. Kuwada, Terry Morgan, Caleb Stepan, Jinqiu Kuang, James Le, Jacques Fantini

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV)-infected patients often develop malabsorption and increased intestinal permeability with diarrhea, called HIV enteropathy, even without enteric opportunistic infections. HIV. gp120-induced calcium signaling, microtubule loss, and physiological changes resembling HIV enteropathy were previously found in the HT-29 intestinal cell line. How gp120 caused these changes was unclear. We show that the HIV co-receptor Bob/GPR15, unlike CCR5 and CXCR4, is abundant at the basal surface of small intestinal epithelium. The gp120-induced effects on HT-29 cells were inhibited by anti-Bob neutralizing antibodies, the selective G protein inhibitor pertussis toxin, and the phospholipase inhibitor U73122, but not neutralizing antibodies to CXCR4. Gp120 strains that induced signaling in HT-29 cells also induced calcium fluxes in Bob-transfected Ghost (3) cells, whereas gp120 strains not activating HT-29 cells also did not activate Bob-transfected cells. Bob is the first HIV co-receptor shown to be abundantly expressed on the basolateral surface of intestinal epithelium. Although Bob is an inefficient infection-inducing co-receptor, it mediates viral strain-specific gp120-induced calcium signaling at low, physiologically reasonable gp120 concentrations, up to 10,000-fold lower gp120 concentrations than the principal co-receptors. Gp120-induced Bob activation is a plausible cause of HIV enteropathy.

Original languageEnglish (US)
Pages (from-to)1933-1939
Number of pages7
JournalAmerican Journal of Pathology
Volume159
Issue number5
StatePublished - 2001
Externally publishedYes

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HIV
HT29 Cells
Virus Receptors
Calcium Signaling
Intestinal Mucosa
Neutralizing Antibodies
Phospholipases
Opportunistic Infections
Pertussis Toxin
GTP-Binding Proteins
Microtubules
Diarrhea
Permeability
Calcium
Cell Line
Infection

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clayton, F., Kotler, D. P., Kuwada, S. K., Morgan, T., Stepan, C., Kuang, J., ... Fantini, J. (2001). Gp120-induced Bob/GPR15 activation: A possible cause of human immunodeficiency virus enteropathy. American Journal of Pathology, 159(5), 1933-1939.

Gp120-induced Bob/GPR15 activation : A possible cause of human immunodeficiency virus enteropathy. / Clayton, Frederic; Kotler, Donald P.; Kuwada, Scott K.; Morgan, Terry; Stepan, Caleb; Kuang, Jinqiu; Le, James; Fantini, Jacques.

In: American Journal of Pathology, Vol. 159, No. 5, 2001, p. 1933-1939.

Research output: Contribution to journalArticle

Clayton, F, Kotler, DP, Kuwada, SK, Morgan, T, Stepan, C, Kuang, J, Le, J & Fantini, J 2001, 'Gp120-induced Bob/GPR15 activation: A possible cause of human immunodeficiency virus enteropathy', American Journal of Pathology, vol. 159, no. 5, pp. 1933-1939.
Clayton, Frederic ; Kotler, Donald P. ; Kuwada, Scott K. ; Morgan, Terry ; Stepan, Caleb ; Kuang, Jinqiu ; Le, James ; Fantini, Jacques. / Gp120-induced Bob/GPR15 activation : A possible cause of human immunodeficiency virus enteropathy. In: American Journal of Pathology. 2001 ; Vol. 159, No. 5. pp. 1933-1939.
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