The HIV-1 Aspartyl Protease: Maturation and Substrate Specificity

Abstract

In all retroviruses, the viral aspartyl protease is first translated as part of a large polyprotein precursor, the 160 kilodalton gag-pol polyprotein in the case of HIV-1 (Rey et al, 1987; Jacks et al, 1988). Experimental evidence strongly suggests that HIV-1 viral particles initially bud out of the host cell with an immature structure and composition, containing unprocessed PrSSgag and Pr160gag-Pol polyproteins (Hockley et al, 1988; Gottlinger et al, 1989, Peng et al, 1989). The question of when and how the protease actually processes these polyproteins is important for the understanding of the viral life cycle but remains to be answered. In an effort to gain information on this process, we undertook a series of genetic studies in Escherichia coli on the maturation of the protease from its precursor forms and on this protease substrate preferences. This information should not only contribute to our understanding of the viral maturation process, but also assist us in the design of inhibitors of this essential viral enzyme.