Immediate and neurotoxic effects of HIV protein gp120 act through CXCR4 receptor

Primary rat hippocampal neurones show pronounced elevations of intracellula r calcium within minutes of exposure to the HIV coat protein gp120. Culture of hippocampal neurones with gp120 causes significant neurotoxicity. We fi nd that the peptide VSLSYRCPCRFF, a competitive inhibitor of the CXCR4 chem okine receptor, markedly inhibits toxicity and eliminates the acute calcium elevation. CXCR4 receptors are thought to signal to the Gi/Go family of tr imeric GTP binding proteins. Pretreatment of hippocampal neurones with pert ussis toxin to inactivate Gi/Go proteins markedly reduced gp120 neurotoxici ty. These results indicate that both short and long term effects of gp120 a re the result of activation of the CXCR4 receptor. (C) 2000 Academic Press.