Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4

Curr Biol. 1998 May 7;8(10):595-8. doi: 10.1016/s0960-9822(98)70230-1.


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 IIB 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.

MeSH terms

  • Apoptosis*
  • Cell Line
  • Chemokine CXCL12
  • Chemokines, CXC / physiology*
  • HIV Envelope Protein gp120 / physiology*
  • HIV-1 / physiology*
  • Humans
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / pathology
  • Receptors, CXCR4 / physiology*


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • HIV Envelope Protein gp120
  • Receptors, CXCR4