Overexpression of human immunodeficiency virus type 1 protease increases intracellular cleavage of Gag and reduces virus infectivity.

Here we have investigated if human immunodeficiency virus type 1 (HIV-1) protease expressed in trans can interfere with production of infectious HIV-1 particles. Protease produced from a Tat and Rev inducible expression plasmid specifically cleaved HIV-1 p55Gag in a dose-dependent manner. Coexpression of protease and an infectious HIV-1 proviral clone resulted in increased intracellular cleavage of p55Gag. As a consequence, virus production and virus infectivity was significantly reduced. These results suggest that overexpression of HIV-1 protease in HIV-1-infected cells is a powerful way to inhibit production of infectious virions.