The neuropathogenesis of HIV-1 infection

HIV infection in brain revolves around productive viral replication in cells of mononuclear phagocyte lineage, including brain macrophages, microglia, and multinucleated giant cells. Together, they are the instigators for cellular and viral neurotoxic activities. Several published reports show that viral and/or cellular products produced from HIV-1-infected macrophages injure neurons and induce glial proliferation during advancing central nervous system (CNS) infection. These findings are supported by the apparent discrepancy between the distribution and numbers of virus-infected cells and concomitant brain tissue pathology. Whether these soluble factors are indirectly responsible for neuronal damage remains undefined. The identification and regulation of neurotoxins produced from HIV-infected macrophages are central to uncovering how HIV mediates CNS disease. The authors who contributed to this work represent laboratories with overlapping areas of expertise. Broad-based complementary hypotheses regarding HIV neuropathogenesis are now provided.