Mutations in the primer grip of human immunodeficiency virus type 1 reverse transcriptase impair proviral DNA synthesis and virion maturation.
This report describes the effects of mutating highly conserved residues in the primer grip domain of human immunodeficiency virus type 1 reverse transcriptase (RT) on virus formation and infectivity. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. Our data indicate that these mutations in RT caused severe defects in proviral DNA synthesis. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160(gag-pol) is of key importance during virus assembly.
LaboRetro, Unité de Virologie Humaine INSERM U412, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
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Ottmann
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Pechoux
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Le Grice
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Darlix
D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000096:biosynthesis*; D015683:Gene Products, gag / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000378:metabolism; D011533:Proviruses / Q000235:genetics; D014771:Virion; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015683:Gene Products, gag; D011498:Protein Precursors; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; C091950:pr160 gag-pol precursor protein, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase