Apoptosis in HIV disease pathogenesis

Abstract Progressive immunosuppression and dementia are associated with human immunodeficiency virus (HIV) infection. These manifestations are a result of apoptosis of T cells in blood and lymphoid tissues and apoptosis of neurons in brain. Apoptosis occurs predominantly in uninfected cells and is driven by viral proteins released by the small numbers of infected cells. These proteins either directly act on lymphocytes and neurons to activate apoptotic pathways or may amplify their response by inducing uninfected macrophages and glial cells to release a number of toxic cellular products and cytokines. These cytokines may also induce HIV replication, thus resulting in positive feed back loops that eventually destroy the immune and nervous systems. Treatment strategies aimed at disrupting these pathways may be useful in acquired immunodeficiency syndrome.