Neuronal glycolytic pathway impairment induced by HIV envenlope glyocprotein gp120

Neurological impairment is a common feature of Acquired Immunodeficiency Sy ndrome (AIDS); functional alterations have been reported both in central an d peripheral nervous system and the Human Immunodeficiency Virus (HIV) enve lope glycoprotein gp120 has been proposed as a neurotoxin acting through a calcium-dependent mechanism. On the other hand it has been reported that gp 120 treatment also induce about a 20% decrease in the cerebral glucose util ization and in the cellular ATP levels. The reported observations were perf ormed on experimental system where also non-neuronal cells where present; i n order to evaluate whether a direct interaction between HIV proteins and n euronal cells takes place, we used a neuroblastoma cultures where only neur onal cells are present. We analysed the effects of gp120 on the N18TG2 neuroblastoma clone. Treatme nts were performed both on growing and confluent cultures. Short time treat ment with gp120 of confluent cultures causes a 25% reduction in the level o f neuron-specific enolase, resulting in a similar decrease of oxygen consum ption. Long time exposure of growing cells also causes a reduction in cell survival. Furthermore, using a membrane-specific fluorescent probe we obser ved that gp120 produces an increase of membrane trafficking. These observat ions suggest a direct interaction between the viral envelope protein and ne uronal cells, which results in an alteration of glycolytic metabolism. This alteration may be related to the neurologic impairments observed in AIDS p atients.