Fig. 6

Role of immunologic NOS (iNOS) in CNS apoptosis of AIDS dementia

The principal cells of the CNS infected by HIV-1 are those of the macrophage/microglia lineage. Infected cells produce viral proteins including gp160 which eventually get cleaved into gp120 and gp41 fragments. gp41 remains membrane bound, whereas gp120 is presumably released into the extracellular milieu. These viral proteins stimulate astrocytes, microglia, and macrophages to secrete cytokines including TNFα and IL-1β. In addition to viral proteins, these cytokines induce the expression of iNOS in these cells, which results in the liberation of nitric oxide (NO). In excessive amounts, NO becomes neurotoxic, inducing cell death pathways including apoptosis.