Banks W A, Akerstrom V, Kastin A J
Veterans Affairs Medical Center and Tulane Univeristy School of Medicine, New Orleans, LA 70146, USA.
J Cell Sci. 1998 Feb;111 ( Pt 4):533-40. doi: 10.1242/jcs.111.4.533.
HIV-1 induces the AIDS dementia complex and infects brain endothelial and glial cells. Because the endothelial cells comprising the blood-brain barrier (BBB) do not possess CD4 receptors or galactosylceramide binding sites, it is unclear how HIV-1 negotiates the BBB. Previous work has suggested that gp120, the glycoprotein viral coat of HIV-1, is capable of inducing adsorptive endocytosis. Glycoprotein lectins like wheatgerm agglutinin induce adsorptive endocytosis and greatly potentiate the uptake by and passage across mouse endothelial cells in vivo and in vitro. We show here that the wheatgerm agglutinin-induced binding of gp120 is dose-dependent and involves components of the cytoskeleton. The uptake is partially dependent on temperature and energy and is modestly enhanced by potassium depletion. Glycosylation of gp120 is critical for its uptake by adsorptive endocytosis since the non-glycosylated form of gp120 is unaffected by wheatgerm agglutinin. Evidence is presented for the existence of a coreceptor sensitive to protamine sulfate that is primarily involved in membrane fusion after 125I-gp120 has bound to the cell membrane and is probably activated after internalization. This coreceptor probably contains a negatively charged heparin sulfate group and could be a member of the chemokine receptor family.
人类免疫缺陷病毒1型（HIV-1）可引发艾滋病痴呆综合征，并感染脑内皮细胞和神经胶质细胞。由于构成血脑屏障（BBB）的内皮细胞不具备CD4受体或半乳糖神经酰胺结合位点，因此尚不清楚HIV-1是如何穿过血脑屏障的。此前的研究表明，HIV-1的糖蛋白病毒包膜gp120能够诱导吸附性胞吞作用。像麦胚凝集素这样的糖蛋白凝集素可诱导吸附性胞吞作用，并在体内和体外极大地增强小鼠内皮细胞的摄取和通过能力。我们在此表明，麦胚凝集素诱导的gp120结合呈剂量依赖性，且涉及细胞骨架成分。摄取部分依赖于温度和能量，钾离子耗竭可适度增强摄取。gp120的糖基化对其通过吸附性胞吞作用的摄取至关重要，因为非糖基化形式的gp120不受麦胚凝集素影响。有证据表明存在一种对硫酸鱼精蛋白敏感的共受体，该共受体主要在125I-gp120与细胞膜结合后参与膜融合，并且可能在内化后被激活。这种共受体可能含有带负电荷的硫酸乙酰肝素基团，可能是趋化因子受体家族的一员。
