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Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.

Publication ,  Journal Article
Dennison, SM; Anasti, KM; Jaeger, FH; Stewart, SM; Pollara, J; Liu, P; Kunz, EL; Zhang, R; Vandergrift, N; Permar, S; Ferrari, G; Tomaras, GD ...
Published in: J Virol
August 2014

UNLABELLED: Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. Disruption of the HIV-1 Env interaction with such alternate receptors could be one strategy to prevent HIV-1 entry through the mucosal barrier. To study antibody modulation of HIV-1 Env-Galcer interactions, we used Galcer-containing liposomes to assess whether natural- and vaccine-induced monoclonal antibodies can block HIV-1 Env binding to Galcer. HIV-1 Env gp140 proteins bound to Galcer liposomes with Kds (dissociation constants) in the nanomolar range. Several HIV-1 ALVAC/AIDSVAX vaccinee-derived monoclonal antibodies (MAbs) specific for the gp120 first constant (C1) region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. Among the C1-specific MAbs that showed Galcer blocking, the antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies. C1-specific IgG monoclonal antibodies that blocked Env binding to Galcer induced upregulation of the gp120 CD4-inducible (CD4i) epitope bound by MAb 17B, demonstrating that a conformational change in gp120 may be required for Galcer blocking. However, the MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 antibody-induced gp120 conformational changes resulted in alteration in a Galcer binding site distant from the CD4i 17B MAb binding site. IMPORTANCE: Galactosyl ceramide, a glycosphingolipid, has been postulated to be a receptor for the HIV-1 envelope glycoprotein (Env) interaction with mucosal epithelial cells. Here, we have mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. Our study revealed that a class of vaccine-induced human antibodies potently blocks HIV-1 Env-Galcer binding by perturbing the HIV-1 Env conformation.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2014

Volume

88

Issue

16

Start / End Page

9406 / 9417

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Protein Binding
  • Liposomes
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Galactosylceramides
 

Citation

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Dennison, S. M., Anasti, K. M., Jaeger, F. H., Stewart, S. M., Pollara, J., Liu, P., … Alam, S. M. (2014). Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. J Virol, 88(16), 9406–9417. https://doi.org/10.1128/JVI.01031-14
Dennison, S Moses, Kara M. Anasti, Frederick H. Jaeger, Shelley M. Stewart, Justin Pollara, Pinghuang Liu, Erika L. Kunz, et al. “Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.J Virol 88, no. 16 (August 2014): 9406–17. https://doi.org/10.1128/JVI.01031-14.
Dennison, S. Moses, et al. “Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.J Virol, vol. 88, no. 16, Aug. 2014, pp. 9406–17. Pubmed, doi:10.1128/JVI.01031-14.
Dennison SM, Anasti KM, Jaeger FH, Stewart SM, Pollara J, Liu P, Kunz EL, Zhang R, Vandergrift N, Permar S, Ferrari G, Tomaras GD, Bonsignori M, Michael NL, Kim JH, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Liao H-X, Haynes BF, Alam SM. Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. J Virol. 2014 Aug;88(16):9406–9417.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2014

Volume

88

Issue

16

Start / End Page

9406 / 9417

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Protein Binding
  • Liposomes
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Galactosylceramides