Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity.
It is generally believed that the gag gene product of human immunodeficiency virus type 1 (HIV-1) is processed into several core proteins by a virus-specific protease. We used deletion mutation analysis to study the role of HIV-specific protease in the processing of core proteins and its requirement for viral infectivity. Several mutant genomes with deletions in the protease gene were constructed. A mammalian cell line, COS-M6, transfected with the wild-type viral genome was shown to produce virions containing processed core proteins, while COS-M6 cells transfected with two mutated genomes could express only the core protein precursor, Pr56gag. The wild-type transfectant produced infectious virus; both transfectants expressing the mutated genomes also produced virions, and one of them still retained reverse transcriptase activity. However, the mutant viral particles were devoid of infectivity. Virions with a distinct central core and an electron-dense nucleoid budded out from the plasma membrane of COS-M6 cells transfected with the wild-type genome. In contrast, noninfectious virions that budded either into cytoplasmic vacuoles or out from the plasma membrane of COS-M6 cells transfected with mutant genomes contained ring-shaped nucleoids. These results indicate that the HIV-1 protease plays a role not only in the maturation of the core proteins but also in the assembly of the virus and thus is required for viral infectivity.
Peng
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Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
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Chang
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Chang
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D005814:Genes, Viral; D016333:HIV Protease; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D014162:Transfection; D014758:Viral Core Proteins / Q000378:metabolism*; D014771:Virion / Q000648:ultrastructure
D004279:DNA, Viral; D014758:Viral Core Proteins; D010450:Endopeptidases; D016333:HIV Protease