Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1α is mediated by the chemokine receptor CXCR4
Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1α is mediated by the chemokine receptor CXCR4
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DOI：
10.1016/s0960-9822(98)70230-1
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发表时间：
1998-05-07
期刊：
影响因子：
9.2
通讯作者：
Horuk, R
中科院分区：
文献类型：
--
作者：
Hesselgesser, J;Taub, D;Horuk, R
CXCR4是一种Cys-X-Cys类趋化因子的七跨膜结构域g蛋白偶联受体，是几种趋化因子受体之一，可作为人类免疫缺陷病毒（HIV-1）糖蛋白gp120的CD4共受体[1-3]。CXCR4可以介导特异性感染T细胞的HIV-1毒株的进入，如IIIB毒株（见[4]综述）。最近的报道表明，gp120可以通过CXCR4[5]发出信号，并且有研究表明，由病毒包膜介导的信号转导可能影响病毒相关的细胞病变或细胞凋亡[6]。神经元凋亡是HIV-1脑感染的一个特征[7,8]，尽管确切的机制尚不清楚。在这里，我们讨论了CXCR4在诱导hNT人神经元细胞系细胞凋亡中的可能作用；这些细胞类似于未成熟的有丝分裂后胆碱能神经元，并具有许多神经元特征[9-15]。我们之前已经发现，来自HIV-1 IIIB菌株的gp120与hNT神经元[15]上表达的CXCR4具有高亲和力，我们现在发现IIIB gp120和Cys-X-Cys趋化因子SDF-1 α可以在缺乏CD4的情况下直接诱导hNT神经元凋亡，并且以剂量依赖的方式。据我们所知，这是首次报道趋化因子和HIV-1包膜糖蛋白通过趋化因子受体引发凋亡反应。(C) Current Biology Ltd . ISSN 0960-9822。
CXCR4, a seven transmembrane domain G-protein-coupled receptor for the Cys-X-Cys class of chemokines, is one of several chemokine receptors that can act as a co-receptor with CD4 for the human immunodeficiency virus (HIV-1) glycoprotein gp120 [1-3]. CXCR4 can mediate the entry of HIV-1 strains that specifically infect T cells, such as the IIIB strain (see [4] for review). Recent reports indicate that gp120 can signal through CXCR4 [5] and it has been suggested that signal transduction, mediated by the viral envelope, might influence viral-associated cytopathicity or apoptosis [6], Neuronal apoptosis is a feature of HIV-1 infection in the brain [7,8], although the exact mechanism is unknown. Here, we address the possible role of CXCR4 in inducing apoptosis using cells of the hNT human neuronal cell line; these cells resemble immature post-mitotic cholinergic neurons and have a number of neuronal characteristics [9-15], We have previously shown that gp120 from the HIV-1 IIIB strain binds with high affinity to CXCR4 expressed on hNT neurons [15], We now find that both IIIB gp120 and the Cys-X-Cys chemokine SDF-1 alpha can directly induce apoptosis in hNT neurons in the absence of CD4 and in a dose-dependent manner. To our knowledge, this is the first report of a chemokine and an HIV-1 envelope glycoprotein eliciting apoptotic responses through a chemokine receptor. (C) Current Biology Ltd ISSN 0960-9822.