Blood-brain barrier changesduring invasion of thecentral nervous system by HIV-1

Abstract.  The mechanism underlyingthe early invasion of thecentral nervous system by HIV-1 isunclear. Here, we summarize oldand new findings supportingblood-brain barrier changes duringHIV and experimental simianimmunodeficiency virus (SIV) infection.The effect of inflammatoryand toxic molecules secreted bymonocytes and microglia on thefunctional integrity of tight junctionsof brain endothelium is highlighted.Furthermore, recent findingson a possible direct role of theenvelope and regulatory HIV-1proteins (gp120, Tat, Nef) in causingthe blood-brain barrierchanges are reviewed. The possibilitythat these proteins, as circulatingmolecules, may bind to microvesselendothelial cells andcause blood-brain changes with nodirect participation of the virus israised. Several issues deserve furtherinvestigation and answers tothese questions may provide keysfor new therapeutic strategies inHIV-1 infection of the central nervoussystem.