IDENTIFICATION OF RESIDUES IN THE N-TERMINAL ACIDIC DOMAIN OF HIV-1 VPR ESSENTIAL FOR VIRION INCORPORATION

Vpr is one of the auxiliary proteins encoded by the HIV-I genome and i s selectively incorporated into the virus particle. It has been shown that Vpr incorporation in the virus particle requires only the core pr otein Gag. In an effort to identify the domains of Vpr which are essen tial for incorporation into the HIV-I virion, site-specific mutagenesi s of vpr was carried out Mutation of the highly conserved acidic resid ues in the N-terminal domain (amino acid positions 17-34) eliminated v irion incorporation. These mutations disrupt a predicted amphipathic a lpha-helical structure that is highly conserved among Vpr sequences. i n contrast, alterations of the conserved cysteine (Cys76), basic domai n (Arg87 and Lys95), and other residues (Gln65) did not impair the inc orporation of Vpr into virus-like particles directed by HIV-1 Gag. The results presented here suggest that protein-protein interactions medi ated through the putative helical domain of Vpr may participate in its incorporation into the virus particle. (C) l995 Academic Press. Inc.