title: Structural variability of env and gag gene products from a highly cytopathic strain of HIV-1.
abstract: The glycoprotein precursor of the highly cytopathic Zairian virus HIV1-NDK synthesized in CEM leukemic cells displayed a molecular mass of 140 kDa (gp140) as compared to the 160 kDa of gp160 of HIV1-LAV prototype strain. This precursor was cleaved to produce a smaller than prototype extra-cellular envelope glycoprotein (gp100) and a transmembrane component with a usual size (gp41). Immunoprecipitates from tunicamycin-treated infected cells demonstrated the presence of a non-glycosylated precursor of 100 kDa for HIV1-LAV prototype strain and 90 kDa for HIV1-NDK. Digestion of labeled precipitates with a mixture of endoglycosidase F and glycopeptidase F reduced the size of HIV1-LAV gp160 and gp120 to 100 and 60 kDa, respectively, while HIV1-NDK gp140 and gp100, after treatment with the same enzymes, displayed an apparent molecular mass of 90 kDa and 55 kDa, respectively. From these data we conclude that HIV1-LAV gp120 and HIV1-NDK gp100 differ both in their proteic moiety (60 kDa and 55 kDa, respectively) and in their carbohydrate moiety (60 kDa and 45 kDa, respectively). These differences could not be deduced from the available gene sequences of the two viruses. A chimeric virus containing the first 124 amino acid residues of the envelope glycoprotein coded by HIV1-LAV sequence and the rest by HIV1-NDK displayed normal size envelope glycoproteins, demonstrating the involvement of this N-terminal sequence in the alteration of the molecular mass characteristic of HIV1-NDK gp140 and gp100. Finally, characterization of the gag gene products from both strains demonstrated that HIV1-NDK p18 and p15 have a slower electrophoretic mobility as compared to its HIV1-LAV counterparts. Therefore, structural properties of HIV1-NDK env and gag products, reflected by their unusual electrophoretic mobilities, may be responsible for HIV1-NDK biological properties.
authors.affiliation: INSERM U 322, Unit of Retrovirus and Associated Diseases, Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Yahi
authors.forename: J
authors.initials: J
authors.lastname: Fantini
authors.forename: I
authors.initials: I
authors.lastname: Hirsch
authors.forename: J C
authors.initials: JC
authors.lastname: Chermann
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006031:Glycosylation; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D014407:Tumor Cells, Cultured
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase