title: Mutations of the human immunodeficiency virus type 1 p6Gag domain result in reduced retention of Pol proteins during virus assembly.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA. xfyu@jhsph.edu
authors.forename: X F
authors.initials: XF
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Dawson
authors.forename: C J
authors.initials: CJ
authors.lastname: Tian
authors.forename: C
authors.initials: C
authors.lastname: Flexner
authors.forename: M
authors.initials: M
authors.lastname: Dettenhofer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D015685:Fusion Proteins, gag-pol / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics* / Q000502:physiology*; D015684:Gene Products, pol / Q000378:metabolism*; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D014771:Virion; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D015684:Gene Products, pol; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease