ENVELOPE GLYCOPROTEIN GP120 OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ALTERS ION-TRANSPORT IN ASTROCYTES - IMPLICATIONS FOR AIDS DEMENTIA COMPLEX

Infection by human immunodeficiency virus type 1 (HIV-1) is often comp licated by a variety of neurological abnormalities. The most common cl inical syndrome, termed acquired immunodeficiency syndrome (AIDS) deme ntia complex, presents as a subcortical dementia with cognitive, motor , and behavioral disturbances and is unique to HIV-1 infection. The pa thogenesis of this syndrome is poorly understood but is believed to in volve interactions among virally infected macrophages/microglia, astro cytes, and neurons. In this study, we show that exposure of primary ra t and human astrocytes to heat-activated HTV-1 virions, or to eukaryot ically expressed HIV-1 and HIV-2 envelope glycoproteins (gp120) stimul ates amiloride-sensitive Na+/H+ antiport, potassium conductance, and g lutamate efflux. These effects are blocked specifically by amiloride, an inhibitor of Na+/H+ antiport and by the selective removal of gp120 with immobilized monoclonal antibody. As a result of modulation of ast rocytic function by gp120, the ensuing neuronal depolarization and glu tamate exposure could activate both voltage-gated and N-methyl-D-aspar tate-regulated Ca2+ channels, leading to increases in intraneuronal Ca 2+ and neuronal death. These findings implicate the astrocyte directly in the pathogenesis of AIDS dementia complex.