HIV-1 TAT INHIBITS THE 20-S PROTEASOME AND ITS 11-S REGULATOR-MEDIATED ACTIVATION

The proteasomal system consists of a proteolytic core, the 20 S protea some, which associates in an ATP-dependent reaction with the 19 S regu latory complex to form the functional 26 S proteasome. In the absence of ATP, the 20 S proteasome forms a complex with the gamma-interferon- inducible 11 S regulator. Both the 20 S proteasome and the 11 S regula tor have been implied in the generation of antigenic peptides. The hum an immunodeficiency virus (HIV)-1 Tat protein causes a number of diffe rent effects during acquired immunodeficiency syndrome (AIDS). Here we show that HIV-1 Tat protein strongly inhibits the peptidase activity of the 20 S proteasome and that it interferes with formation of the 20 S proteasome-11 S regulator complex. In addition, it slightly increas es the activity of purified 26 S proteasome. These results may explain the mechanism by which HIV-1-infected cells escape cytotoxic T lympho cyte response and at least in part immunodeficiency in AIDS patients.