Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein

The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is l ocated between the structural and enzymatic domains of the Gag-Pol polyprot ein, Banked by the nucleocapsid (NC) and the protease (PR) domain at its am ino and carboxyl termini, respectively. Here, we report that recombinant hi ghly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kin etic analyses and cross-linking experiments revealed a competitive mechanis m for PR inhibition by p6*. We further demonstrate that the four carboxyl-t erminal residues of p6* are essential but not sufficient for p6*-mediated i nhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replica tion.