Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition

Milan Raska, Kazuo Takahashi, Lydie Czernekova, Katerina Zachova, Stacy Hall, Zina Moldoveanu, Matt C. Elliott, Landon Wilson, Rhubell Brown, Dagmar Jancova, Stephen Barnes, Jana Vrbkova, Milan Tomana, Phillip D. Smith, Jiri Mestecky, Matthew B. Renfrow, Jan Novak

Research output: Contribution to journalArticle

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Abstract

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 immunerecognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed anewapproach to characterize cellspecific 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.

Original languageEnglish
Pages (from-to)20860-20869
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number27
DOIs
Publication statusPublished - 02-07-2010

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Glycosylation
Viruses
HIV-1
Polysaccharides
Antibodies
Virus Internalization
Molecular mass
Mannose
Epitopes
Glycoproteins
Vaccination
Vaccines
Cells
Cell Line
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Raska, Milan ; Takahashi, Kazuo ; Czernekova, Lydie ; Zachova, Katerina ; Hall, Stacy ; Moldoveanu, Zina ; Elliott, Matt C. ; Wilson, Landon ; Brown, Rhubell ; Jancova, Dagmar ; Barnes, Stephen ; Vrbkova, Jana ; Tomana, Milan ; Smith, Phillip D. ; Mestecky, Jiri ; Renfrow, Matthew B. ; Novak, Jan. / Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 27. pp. 20860-20869.
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abstract = "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 immunerecognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed anewapproach to characterize cellspecific 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.",
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Raska, M, Takahashi, K, Czernekova, L, Zachova, K, Hall, S, Moldoveanu, Z, Elliott, MC, Wilson, L, Brown, R, Jancova, D, Barnes, S, Vrbkova, J, Tomana, M, Smith, PD, Mestecky, J, Renfrow, MB & Novak, J 2010, 'Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition', Journal of Biological Chemistry, vol. 285, no. 27, pp. 20860-20869. https://doi.org/10.1074/jbc.M109.085472

Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition. / Raska, Milan; Takahashi, Kazuo; Czernekova, Lydie; Zachova, Katerina; Hall, Stacy; Moldoveanu, Zina; Elliott, Matt C.; Wilson, Landon; Brown, Rhubell; Jancova, Dagmar; Barnes, Stephen; Vrbkova, Jana; Tomana, Milan; Smith, Phillip D.; Mestecky, Jiri; Renfrow, Matthew B.; Novak, Jan.

In: Journal of Biological Chemistry, Vol. 285, No. 27, 02.07.2010, p. 20860-20869.

Research output: Contribution to journalArticle

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T1 - Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition

AU - Raska, Milan

AU - Takahashi, Kazuo

AU - Czernekova, Lydie

AU - Zachova, Katerina

AU - Hall, Stacy

AU - Moldoveanu, Zina

AU - Elliott, Matt C.

AU - Wilson, Landon

AU - Brown, Rhubell

AU - Jancova, Dagmar

AU - Barnes, Stephen

AU - Vrbkova, Jana

AU - Tomana, Milan

AU - Smith, Phillip D.

AU - Mestecky, Jiri

AU - Renfrow, Matthew B.

AU - Novak, Jan

PY - 2010/7/2

Y1 - 2010/7/2

N2 - 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 immunerecognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed anewapproach to characterize cellspecific 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.

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