NEURONAL APOPTOSIS INDUCED BY HIV-1 GP120 AND THE CHEMOKINE SDF-1-ALPHA IS MEDIATED BY THE CHEMOKINE RECEPTOR CXCR4

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 stra in (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 cyto pathicity or apoptosis [6], Neuronal apoptosis is a feature of HIV-1 i nfection in the brain [7,8], although the exact mechanism is unknown. Here, we address the possible role of CXCR4 in inducing apoptosis usin g cells of the hNT human neuronal cell line; these cells resemble imma ture post-mitotic cholinergic neurons and have a number of neuronal ch aracteristics [9-15], We have previously shown that gp120 from the HIV -1 IIIB strain binds with high affinity to CXCR4 expressed on hNT neur ons [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 absen ce of CD4 and in a dose-dependent manner. To our knowledge, this is th e first report of a chemokine and an HIV-1 envelope glycoprotein elici ting apoptotic responses through a chemokine receptor. (C) Current Bio logy Ltd ISSN 0960-9822.