NeuroAIDS: Contributions of the human immunodeficiency virus-1 proteins Tat and gp120 as well as CD40 to microglial activation

Microglia are the resident phagocytes of the brain and are an important source of proinflammatory mediators. Human immunodeficiency virus (HIV)-1 infects the central nervous system early in the course of disease, and it is believed that this occurs, in part, through the transmigration of HIV-1-infected cells across the blood-brain barrier. Infected cells release viral proteins, such as Tat and gp120. After microglia interact with these proteins, they become activated and secrete chemokines; upregulate key surface receptors, such as CD40, and also activate resident cells. This review focuses on the consequences of microglial activation in NeuroAIDS, with an emphasis on chemokine production and CD40 upregulation after interaction with tat or gp120. The importance of microglial CD40 in two other neurological diseases, Alzheimer's disease and multiple sclerosis, is also discussed.