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Glycosylation Patterns of HIV-1 gp120 Depend on the Type of Expressing Cells and Affect Antibody Recognition

2010; Elsevier BV; Volume: 285; Issue: 27 Linguagem: Inglês

10.1074/jbc.m109.085472

1083-351X

Milan Raška, Kazuo Takahashi, Lýdie Czerneková, Kateřina Zachová, Stacy Hall, Zina Moldoveanu, Matt C. Elliott, Landon Wilson, Rhubell Brown, Dagmar Jancova, Stephen Barnes, Jana Vrbková, Milan Tomana, Phillip D. Smith, Jiří Městecký, Matthew B. Renfrow, Jan Novák,

Monoclonal and Polyclonal Antibodies Research

Human immunodeficiency virus type 1 (HIV-1) entry is mediated by the interaction between a variably glycosylated envelope glycoprotein (gp120) and host-cell receptors. Approximately half of the molecular mass of gp120 is contributed by N -glycans, which serve as potential epitopes and may shield gp120 from immune recognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed a new approach to characterize cell-specific gp120 glycosylation, the regulation of glycosylation, and the effect of variable glycosylation on antibody reactivity. A model oligomeric gp120 was expressed in different cell types, including cell lines that represent host-infected cells or cells used to produce gp120 for vaccination purposes. N -Glycosylation of gp120 varied, depending on the cell type used for its expression and the metabolic manipulation during expression. The resultant glycosylation included changes in the ratio of high-mannose to complex N -glycans, terminal decoration, and branching. Differential glycosylation of gp120 affected envelope recognition by polyclonal antibodies from the sera of HIV-1-infected subjects. These results indicate that gp120 glycans contribute to antibody reactivity and should be considered in HIV-1 vaccine design.