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Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.

Publication ,  Journal Article
Martin, G; Burke, B; Thaï, R; Dey, AK; Combes, O; Ramos, OHP; Heyd, B; Geonnotti, AR; Montefiori, DC; Kan, E; Lian, Y; Sun, Y; Abache, T ...
Published in: J Biol Chem
June 17, 2011

CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477-17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

June 17, 2011

Volume

286

Issue

24

Start / End Page

21706 / 21716

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Receptors, CCR5
  • Protein Conformation
  • Protein Binding
  • HIV-1
  • HIV Envelope Protein gp120
  • Disulfides
  • Cysteine
  • Cross-Linking Reagents
  • Cricetulus
 

Citation

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MLA
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Martin, G., Burke, B., Thaï, R., Dey, A. K., Combes, O., Ramos, O. H. P., … Martin, L. (2011). Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic. J Biol Chem, 286(24), 21706–21716. https://doi.org/10.1074/jbc.M111.232272
Martin, Grégoire, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Oscar H. P. Ramos, Bernadette Heyd, et al. “Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.J Biol Chem 286, no. 24 (June 17, 2011): 21706–16. https://doi.org/10.1074/jbc.M111.232272.
Martin G, Burke B, Thaï R, Dey AK, Combes O, Ramos OHP, et al. Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic. J Biol Chem. 2011 Jun 17;286(24):21706–16.
Martin, Grégoire, et al. “Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.J Biol Chem, vol. 286, no. 24, June 2011, pp. 21706–16. Pubmed, doi:10.1074/jbc.M111.232272.
Martin G, Burke B, Thaï R, Dey AK, Combes O, Ramos OHP, Heyd B, Geonnotti AR, Montefiori DC, Kan E, Lian Y, Sun Y, Abache T, Ulmer JB, Madaoui H, Guérois R, Barnett SW, Srivastava IK, Kessler P, Martin L. Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic. J Biol Chem. 2011 Jun 17;286(24):21706–21716.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

June 17, 2011

Volume

286

Issue

24

Start / End Page

21706 / 21716

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Receptors, CCR5
  • Protein Conformation
  • Protein Binding
  • HIV-1
  • HIV Envelope Protein gp120
  • Disulfides
  • Cysteine
  • Cross-Linking Reagents
  • Cricetulus