title: Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1.
abstract: We describe mutants of human immunodeficiency virus type-1 (HIV-1) strain NL4-3, which are lacking the thirteenth, fifteenth, or seventeenth sites for N-linked glycosylation (g13, g15, g17) of the envelope protein gp120. All three sites are located within the hypervariable V3 loop region of gp120. Those mutants lacking carbohydrates g15 or combinations of g15/g17 showed markedly higher infectivity for GHOST cells (human osteosarcoma cells) expressing CXCR4 (GHOST-X4), compared to the fully glycosylated NL4-3 wild type virus. In addition, these mutants could also infect cells which exhibits low background expression of CXCR4, corresponding to <10% of that observed for GHOST-X4 cells. In addition to the enhanced infectivity observed, mutants lacking g15 and g17 showed increased resistance to inhibition by SDF-1, the natural ligand of CXCR4. Thus, loss of the oligosaccharides g15 and g17 in the V3 region of gp120 markedly influences CXCR4-specific infection.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Strasse 75, 20359 Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Polzer
authors.forename: M T
authors.initials: MT
authors.lastname: Dittmar
authors.forename: H
authors.initials: H
authors.lastname: Schmitz
authors.forename: B
authors.initials: B
authors.lastname: Meyer
authors.forename: H
authors.initials: H
authors.lastname: Müller
authors.forename: H G
authors.initials: HG
authors.lastname: Kräusslich
authors.forename: M
authors.initials: M
authors.lastname: Schreiber
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D011134:Polysaccharides / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014774:Virulence / Q000235:genetics
chemical_list: D017931:DNA Primers; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011134:Polysaccharides