Intracellular calcium release induced by human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein in human intestinal epithelial cells: a putative mechanism for HIV-1 enteropathy.
Intracellular Ca2+ ([Ca2+]i) was measured in single human epithelial intestinal HT-29-D4 cells with the Ca2+ probe Fura-2 and digital imaging microscopy. Treatment of these cells with HIV-1 surface envelope glycoprotein gp120 (or a soluble form of its precursor gp160) induced an important increase of [Ca2+]i. This effect was abolished by preincubation of the viral glycoprotein with neutralizing antibodies specific for the V3 domain of gp120. These antibodies inhibited the binding of both gp120 and gp160 to galactosylceramide (GalCer), the alternative HIV-1 receptor in HT-29-D4 cells. Moreover, treatment of HT-29-D4 cells with an anti-GalCer mAb induced an increase in [Ca2+]i and rendered the cells insensitive to HIV-1 glycoprotein stimulation. The calcium response resulted from release of Ca2+ from caffeine-sensitive intracellular stores. Finally, the viral glycoprotein specifically abrogated the calcium response to the neuropeptide agonist neurotensin, a stimulator of chloride secretion via inositol trisphosphate-mediated calcium mobilization. Reciprocally, after neurotensin stimulation, the cells did not respond to gp120, showing that neurotensin and gp120 stimulate a common pathway of [Ca2+]i mobilization. These results suggest that HIV-1 may directly alter ion secretion in the intestine and thus be the causative agent of the watery diarrhea associated with HIV-1 infection.
Dayanithi
G
G
Laboratoire de Neurobiologie Endocrinologique, CNRS URA 1197, Université Montpellier 2, France.
Yahi
N
N
Baghdiguian
S
S
Fantini
J
J
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004751:Enteritis / Q000209:etiology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005699:Galactosylceramides / Q000378:metabolism; D015686:Gene Products, env / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000150:complications; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D007424:Intracellular Fluid / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
D005699:Galactosylceramides; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011994:Recombinant Proteins; D002118:Calcium