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 Scopus citations

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
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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