CELLULAR ASPECTS OF HIV-1 INFECTION OF MACROPHAGES LEADING TO NEURONAL DYSFUNCTION IN IN-VITRO MODELS FOR HIV-1 ENCEPHALITIS

HIV-1 is a hematogenously spread virus that most likely gains entry in to the brain within blood-derived macrophages. Indeed, productive vira l replication selectively occurs within perivascular and parenchymal b lood-derived macrophages and microglia and HN-infected macrophages hav e increased potential to bind and transmigrate through the blood-brain barrier. Once inside the brain, HIV-infected macrophages secrete a va riety of pro-inflammatory mediators that display neuromodulatory and n eurotoxic activities in several in vitro models for HIV-1 encephalitis . The final outcome regarding neuronal function and cell loss is regul ated through intercellular interactions between these virus-infected c ells and astrocytes, In this regard, both HIV-induced intracellular ev ents in macrophages and interactions between HIV-infected macrophages and brain cells are reviewed as factors that might lead to neuronal in jury in in vitro model systems for HIV-1 encephalitis.