Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity

Abstract

The human immunodeficiency virus type 1 (HIV‐1) protein Tat is known to be released from HIV‐1‐infected cells. We show that micromolar concentrations of Tat depolarized young rat and adult human neurons. In addition, Tat, at similar concentrations, was toxic to human fetal neurons in culture. Tat‐induced responses were insensitive to the Na⁺ channel blocker tetrodotoxin, suggesting a direct effect of Tat on neurons. Tat‐induced depolarizations and cytotoxicity were blocked by the excitatory amino acid antagonist kynurenate. The N‐methylvD‐aspartate receptor antagonist Dv2vaminov5‐phosphonovalerate had little effect on Tatvinduced depolarizations but did provide protection from Tat neurotoxicity. These results suggest that Tat, released from HIVv1vinfected cells, may be an important mediator of neurotoxicity observed in HIV1 encephalopathy.