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Title: Mutations of the human immunodeficiency virus type 1 p6Gag domain result in reduced retention of Pol proteins during virus assembly.

Authors: Yu, X F; Dawson, L; Tian, C J; Flexner, C; Dettenhofer, M

Published In J Virol, (1998 Apr)

Abstract: One of the crucial steps in the assembly of the human immunodeficiency virus type 1 (HIV-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 initially synthesized as Gag-Pol fusion polyproteins. It has been shown that the incorporation of Gag-Pol polyproteins during virus assembly requires the Gag domains that are shared by the Gag and Gag-Pol precursors. 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 precursor, drastically reduced the amount of Pol proteins in the mutant virions. Mutations in the lentivirus conserved motif P(T/S)APP in p6 also 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 incorporation of unprocessed Gag-Pol precursors into p6 mutant virions was detected when the viral protease was mutated, suggesting that the interactions among mutant Gag molecules and Gag-Pol precursors were not significantly affected. These results suggest that the p6 domain of HIV-1 Gag may play an important role in recruiting or retaining cleaved Pol proteins during virus assembly.

PubMed ID: 9525672 Exiting the NIEHS site

MeSH Terms: Amino Acid Sequence; Animals; Base Sequence; Binding Sites; COS Cells; Fusion Proteins, gag-pol/metabolism; Gene Products, gag/genetics*; Gene Products, gag/physiology*; Gene Products, pol/metabolism*; HIV Protease/genetics; HIV Protease/metabolism; HIV Reverse Transcriptase/metabolism; HIV-1/genetics; HIV-1/metabolism; HIV-1/physiology*; Humans; Intracellular Fluid/metabolism; Molecular Sequence Data; Mutagenesis; Mutation*; Point Mutation; Protein Processing, Post-Translational; Virion; Virus Assembly*; gag Gene Products, Human Immunodeficiency Virus

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