HIV-1 Coat Protein GP120 Induces Neuronal Injury to Cultured Dopamine Cells

Abstract

Human immunodeficiency virus (HIV)-1 infection is commonly associated with neurological manifestations that can produce devastating cognitive and motor impairments.^1–4 Concomitant with this are CNS disturbances which can include various organic mental disorders.⁵ These CNS disturbances may occur in the absence of opportunistic infections as well as in the absence of direct infection of neurons by HIV-1.⁴ In fact, HIV-1 has only been demonstrated in macrophage or microglial cells and not in neurons.^6–9 Previous studies have shown that infection with HIV-1 results in neurotoxicity which can be elicited by viral particles, the most likely of which is the glycoprotein, gp120.^10–12 This viral protein has been shown to produce neurotoxicity at very low concentrations (pM) in various neuronal culture systems^10–19 as well as modify astrocyte function.^20–22 The mechanism(s) by which gp 120 induces neurotoxicity are not understood, but there is evidence that NMDA receptors, Ca²⁺ channels, and nitric oxide (NO) are important mediators.^{11,13–15,18,19}