Chemokines and Their Receptors and the Neuropathogenesis of HIV-1 Infection

Infection of the central nervous system (CNS) by the human immunodeficiency virus (HIV) causes a broad spectrum of behavioral, motor, and cognitive dysfunctions. In its most severe form, HIV-1-associated dementia or HAD, occurs late in viral infection, often associated with profound immunosuppression. Disease is perpetuated by cellular and viral neurotoxins produced from brain mononuclear phagocytes (MP; macrophages and microglia) without direct infection of neurons. Such MP neurotoxins are, in measure, homeostatic immune products that negatively affect neuronal function when produced in abundance. Induction of disease through metabolic events perpetrated by pro-inflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinc acid, glutamate viral structural, and regulatory proteins makes the neuropathogenesis of HIV infection unique.