INFECTION OF COLONIC EPITHELIAL-CELL LINES BY TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS IS ASSOCIATED WITH CELL-SURFACE EXPRESSION OF GALACTOSYLCERAMIDE, A POTENTIAL ALTERNATIVE GP120 RECEPTOR
INFECTION OF COLONIC EPITHELIAL-CELL LINES BY TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS IS ASSOCIATED WITH CELL-SURFACE EXPRESSION OF GALACTOSYLCERAMIDE, A POTENTIAL ALTERNATIVE GP120 RECEPTOR
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DOI：
10.1073/pnas.90.7.2700
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发表时间：
1993-04-01
影响因子：
11.1
通讯作者：
GONZALEZSCARANO, F
中科院分区：
文献类型：
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作者：
FANTINI, J;COOK, DG;GONZALEZSCARANO, F
胃肠道在1型人类免疫缺陷病毒（HIV-1）感染的发病机制和病理生理学中起主要作用。它是病毒进入的潜在途径，也是许多并发症的发生部位，包括机会性感染和原发性HIV诱导的肠病。相应地，体内和体外研究都证明了淋巴和上皮来源的胃肠道细胞的HIV感染。HT-29是一种可感染多种HIV-1毒株的人结肠上皮细胞系，不表达CD 4蛋白或mRNA。最近的研究表明，识别HT-29细胞中与半乳糖神经酰胺（GalCer）相关的中性糖脂的抗体抑制了该细胞系的HIV-1感染，扩展了以前在神经细胞中的发现。在目前的研究中，我们进一步分析了HT-29细胞的中性糖脂，并表明它们含有真正的GalCer，重组gp 120结合到这种糖脂。此外，通过分析来自HT-29和Caco-2（另一种人结肠细胞系）的克隆中的GalCer表达，我们观察到这种糖脂的表达水平与对HIV-1感染的敏感性相关。Caco-2的亚克隆不表达GalCer，并且不受三种HIV-1毒株中任何一种的感染。这些结果加强了GalCer是CD 4-细胞系中的替代受体的可能性。此外，由于GalCer是小肠和结肠上皮细胞中的主要糖脂，因此这些结果为HIV-1与胃肠道上皮细胞的结合以及病毒进入这些细胞提供了结构基础。
The gastrointestinal tract plays a major role in the pathogenesis and pathophysiology of infection by the type 1 human immunodeficiency virus (HIV-1). It is a potential route for viral entry and it is the site of a number of complications, including both opportunistic infections and a primary HIV-induced enteropathy. Correspondingly, both in vivo and in vitro studies have demonstrated HIV infection of gastrointestinal cells of lymphoid and epithelial origin. HT-29, a human colonic epithelial cell line that is infectable with many HIV-1 strains, does not express CD4 protein or mRNA. Recent studies showed that antibodies recognizing a neutral glycolipid related to galactosylceramide (GalCer) in HT-29 cells inhibited HIV-1 infection of this cell line, extending previous findings in neural cells. In the current studies, we further analyzed the neutral glycolipids of HT-29 cells and showed that they contained authentic GalCer and that recombinant gp120 bound to this glycolipid. Moreover, by analyzing GalCer expression in clones derived from HT-29 and Caco-2 (another human colonic cell line), we observed that the level of expression of this glycolipid was associated with the sensitivity to HIV-1 infection. Subclones of Caco-2 did not express GalCer and were not infectable with any of three HIV-1 strains. These results strengthen the possibility that GalCer is an alternative receptor in CD4- cell lines. Furthermore, since GalCer is a major glycolipid in epithelial cells of the small intestine and colon, these results provide a structural basis for the binding of HIV-1 by gastrointestinal epithelial cells and the entry of the virus into those cells.