title: Direct effect of type 1 human immunodeficiency virus (HIV-1) on intestinal epithelial cell differentiation: relationship to HIV-1 enteropathy.
abstract: Human immunodeficiency virus (HIV)-infected patients display severe impairments of gastrointestinal functions, including diarrhea and malabsorption, even in the absence of opportunistic infections. Since HIV-1 proteins and nucleic acids have been detected in several cell types of the intestinal mucosa, it has been postulated that HIV-1 itself could alter enterocytic functions. In the present study, we analyzed the effect of HIV-1 on the differentiation process of the epithelial intestinal cell clone HT-29-D4, which mimics the maturation of enterocytes along the crypt-villus axis of the small intestine. We found that HIV-1 infection impairs cellular differentiation (i) by affecting the barrier function of the epithelium, as evidenced by a decrease in the transepithelial electrical resistance, and (ii) by inhibiting the activity of one major glucose absorption function, i.e., sodium/glucose cotransport. At the morphological level, HIV-1 infection of HT-29-D4 cells was associated with the formation of lumina, which are representative of a defect in cellular organization. These morphofunctional perturbations induced by HIV-1 could be mimicked by nocodazole, a microtubule-disrupting agent. Correspondingly, HIV-1 exposure of HT-29-D4 cells evoked a massive disruption of microtubules, as revealed by alpha-tubulin indirect immunofluorescence staining. A similar effect was observed after incubation of the cells with either recombinant gp120 or a monoclonal antibody against galactosylceramide (GalCer), the intestinal receptor for HIV-1 gp120, suggesting that the effect of HIV-1 was mediated by the binding of gp120 to GalCer. Based on these data, we propose that HIV-1 may selectively alter enterocytic functions through a direct effect on the intracellular architecture of the cells. In contrast with previous theories for HIV-1 enteropathy, our data support the concept that HIV-1 may perturb intestinal functions without necessarily infecting intestinal epithelial cells.
authors.affiliation: Laboratoire de Biochimie et Biologie de la Nutrition, UPRESA-CNRS 6033, Faculté des Sciences de St Jérôme, Marseille.
authors.forename: O
authors.initials: O
authors.lastname: Delézay
authors.forename: N
authors.initials: N
authors.lastname: Yahi
authors.forename: C
authors.initials: C
authors.lastname: Tamalet
authors.forename: S
authors.initials: S
authors.lastname: Baghdiguian
authors.forename: J A
authors.initials: JA
authors.lastname: Boudier
authors.forename: J
authors.initials: J
authors.lastname: Fantini
mesh_terms: D002454:Cell Differentiation; D003847:Deoxyglucose / Q000378:metabolism; D004594:Electrophysiology; D015497:HIV-1 / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D008757:Methylglucosides / Q000493:pharmacokinetics; D008870:Microtubules / Q000648:ultrastructure / Q000821:virology; D014404:Tubulin / Q000378:metabolism
chemical_list: D008757:Methylglucosides; D014404:Tubulin; C027020:methylglucoside; D003847:Deoxyglucose