HIV-1 Tat protein and endothelium: from protein/cell interaction to AIDS-associated pathologies

Tat protein, the transactivating factor of the human immunodeficiency virus type 1 (HIV-1), is a small cationic polypeptide that can be released from HIV-1 infected cells. Extracellular Tat elicits different biological responses in several types of target cells, including endothelial cells (ECs). In the present paper, we will review the various aspects from the laboratory bench to the bedside that characterize the tight relationship that exists between HIV-1 Tat and the endothelium. Tat interacts with at least three different types of receptors present on the surface of ECs. This leads to the activation of several signal transduction pathways and triggers various biological responses in the endothelium. The bioavailability, cell interaction, intracellular signaling, and biological activity of Tat are tightly regulated by components of the extracellular matrix and circulating molecules. Thus, Tat is at the center of a complex network of interactions that occur at the surface of ECs and that greatly affect the functions of the endothelium, possibly resulting in some of the pathological processes that occur in AIDS patients.