Direct effect of type 1 human immunodeficiency virus (HIV-I) on intestinal epithelial cell differentiation: Relationship to HIV-I enteropathy
Direct effect of type 1 human immunodeficiency virus (HIV-I) on intestinal epithelial cell differentiation: Relationship to HIV-I enteropathy
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DOI：
10.1006/viro.1997.8829
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发表时间：
1997-11-24
期刊：
影响因子：
3.7
通讯作者：
Fantini, J
中科院分区：
文献类型：
--
作者：
Delezay, O;Yahi, N;Fantini, J
人类免疫缺陷病毒（HIV）感染的患者即使在没有机会性感染的情况下也表现出严重的胃肠道功能损害，包括腹泻和吸收不良。由于在肠粘膜的几种细胞类型中检测到HIV-I蛋白和核酸，因此推测HIV-I本身可以改变肠细胞功能。在本研究中，我们分析了HIV-I对上皮细胞[肠细胞克隆HT-29-D4]分化过程的影响，该细胞克隆模仿肠上皮细胞沿着小肠的隐窝-绒毛轴的成熟。我们发现，HIV-1感染损害细胞分化（i）通过影响上皮的屏障功能，如跨上皮电阻的降低所证明的，和（ii）通过抑制一种主要葡萄糖吸收功能的活性，即，钠/葡萄糖共转运在形态学水平，HT-29-D4细胞的HIV-1感染与管腔的形成有关，管腔是细胞组织缺陷的代表。HIV-1诱导的这些形态功能紊乱可以被微管破坏剂诺考达唑模拟。相应地，如α-微管蛋白间接免疫荧光染色所示，HT-29-D4细胞的HIV-1暴露引起微管的大量破坏。在将细胞与重组gp 120或抗半乳糖神经酰胺（GalCer）（HIV-1 gp 120的肠道受体）的单克隆抗体孵育后观察到类似的效果，这表明HIV-1的效果是由gp 120与GalCer的结合介导的。基于这些数据，我们提出，HIV-1可能通过直接影响细胞的细胞内结构来选择性地改变肠细胞的功能。与以前的HIV-I肠病理论相反，我们的数据支持HIV-I可能扰乱肠功能而不一定感染肠上皮细胞的概念。(C)1997年学术出版社。
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-I proteins and nucleic acids have been detected in several cell types of the intestinal mucosa, it has been postulated that HIV-I itself could alter enterocytic functions. In the present study, we analyzed the effect of HIV-I on the differentiation process of the epithelia[ 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-I 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-I may selectively alter enterocytic functions through a direct effect on the intracellular architecture of the cells. in contrast with previous theories for HIV-I enteropathy, our data support the concept that HIV-I may perturb intestinal functions without necessarily infecting intestinal epithelial cells. (C) 1997 Academic Press.