MUTATIONS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 P6(GAG) DOMAIN RESULT IN REDUCED RETENTION OF POL PROTEINS DURING VIRUS ASSEMBLY

One of the crucial steps in the assembly of the human immunodeficiency virus type 1 (HPV-1) and other retroviruses is the incorporation and retention of all the key viral enzymes in released virions. The viral enzymes protease, reverse transcriptase, and integrase of HIV-1 are in itially synthesized as Gag-Pol fusion polyproteins. It has been shown that the incorporation of Gag-Pol polyproteins during virus assembly r equires the Gag domains that are shared by the Gag and Gag-Pol precurs ors. We now report that truncation of the C-terminal p6 domain of HIV- 1 Gag, which is present in the Gag precursor but not in the Gag-Pol pr ecursor, drastically reduced the amount of Pol proteins in the mutant virions. Mutations in the lentivirus conserved motif P(T/S)APP in p6 a lso drastically reduced the amount of Pol proteins in mutant virions. The steady-state levels of Gag-Pol precursors and cleaved Pol proteins in the transfected cells were not affected by mutations in p6. The in corporation of unprocessed Gag-Pol precursors into p6 mutant virions w as detected when the viral protease was mutated, suggesting that the i nteractions among mutant Gag molecules and Gag-Pol precursors were not significantly affected. These results suggest that the p6 domain of H IV-1 Gag may play an important role in recruiting or retaining cleaved Pol proteins during virus assembly.