Role of the C terminus Gag protein in human immunodeficiency virus type 1 virion assembly and maturation.
Lentiviral Gag polyproteins have a proline-rich protein, p6, at their C terminus. There are conflicting reports about the function of p6 in virus release. In the present work, mutants that affect p6 of human immunodeficiency virus type 1 (HIV-1) Gag polyprotein were constructed and analysed. None of the mutants prevented virus release completely; however, detachment of budding particles was less efficient as evidenced by electron microscopy. Virions of the p6 truncation mutant B2TAA had a significantly reduced number of Pol proteins (p66, p51 and p34) and an increased amount of incompletely processed Gag proteins compared with the parental virus. A mutation that altered the cleavage site between p6 and p1 did not significantly affect virus assembly, virus release or protein processing with the exception of cleavage between p6 and p1. However, virions of this mutant (B2P6C) exhibited irregular-shaped core structures that were distinct from the cone-shaped core structure seen in the parental virion. B2P6C mutant virus was non-infectious in CD4+ T cells. These results suggest that mutations in p6 affect efficient detachment of budding particles from the cell surface. Proper cleavage between p6 and p1 may be critical for the formation of the distinctive cone-shaped core structure of HIV-1 virions.
Yu
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Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Matsuda
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Yu
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QC
Lee
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Essex
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D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015683:Gene Products, gag / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015684:Gene Products, pol / Q000032:analysis; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics; D011499:Protein Processing, Post-Translational; D050378:T-Lymphocytes, Regulatory / Q000821:virology; D014771:Virion / Q000737:chemistry / Q000648:ultrastructure; D019065:Virus Assembly / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015684:Gene Products, pol; D011498:Protein Precursors; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus; C083002:p6 gag protein, Human immunodeficiency virus 1