TY - JOUR
T1 - Gp120-induced Bob/GPR15 activation
T2 - A possible cause of human immunodeficiency virus enteropathy
AU - Clayton, Frederic
AU - Kotler, Donald P.
AU - Kuwada, Scott K.
AU - Morgan, Terry
AU - Stepan, Caleb
AU - Kuang, Jinqiu
AU - Le, James
AU - Fantini, Jacques
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)63040-4
DO - 10.1016/S0002-9440(10)63040-4
M3 - Article
C2 - 11696454
AN - SCOPUS:0035156681
SN - 0002-9440
VL - 159
SP - 1933
EP - 1939
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -