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Role of HIV membrane in neutralization by two broadly neutralizing antibodies.

Publication ,  Journal Article
Alam, SM; Morelli, M; Dennison, SM; Liao, H-X; Zhang, R; Xia, S-M; Rits-Volloch, S; Sun, L; Harrison, SC; Haynes, BF; Chen, B
Published in: Proc Natl Acad Sci U S A
December 1, 2009

Induction of effective antibody responses against HIV-1 infection remains an elusive goal for vaccine development. Progress may require in-depth understanding of the molecular mechanisms of neutralization by monoclonal antibodies. We have analyzed the molecular actions of two rare, broadly neutralizing, human monoclonal antibodies, 4E10 and 2F5, which target the transiently exposed epitopes in the membrane proximal external region (MPER) of HIV-1 gp41 envelope during viral entry. Both have long CDR H3 loops with a hydrophobic surface facing away from the peptide epitope. We find that the hydrophobic residues of 4E10 mediate a reversible attachment to the viral membrane and that they are essential for neutralization, but not for interaction with gp41. We propose that these antibodies associate with the viral membrane in a required first step and are thereby poised to capture the transient gp41 fusion intermediate. These results bear directly on strategies for rational design of HIV-1 envelope immunogens.

Duke Scholars

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 1, 2009

Volume

106

Issue

48

Start / End Page

20234 / 20239

Location

United States

Related Subject Headings

  • Viral Vaccines
  • Protein Binding
  • Neutralization Tests
  • Mutation
  • Models, Molecular
  • Membranes, Artificial
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp41
 

Citation

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Alam, S. M., Morelli, M., Dennison, S. M., Liao, H.-X., Zhang, R., Xia, S.-M., … Chen, B. (2009). Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci U S A, 106(48), 20234–20239. https://doi.org/10.1073/pnas.0908713106
Alam, S Munir, Marco Morelli, S Moses Dennison, Hua-Xin Liao, Ruijun Zhang, Shi-Mao Xia, Sophia Rits-Volloch, et al. “Role of HIV membrane in neutralization by two broadly neutralizing antibodies.Proc Natl Acad Sci U S A 106, no. 48 (December 1, 2009): 20234–39. https://doi.org/10.1073/pnas.0908713106.
Alam SM, Morelli M, Dennison SM, Liao H-X, Zhang R, Xia S-M, et al. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20234–9.
Alam, S. Munir, et al. “Role of HIV membrane in neutralization by two broadly neutralizing antibodies.Proc Natl Acad Sci U S A, vol. 106, no. 48, Dec. 2009, pp. 20234–39. Pubmed, doi:10.1073/pnas.0908713106.
Alam SM, Morelli M, Dennison SM, Liao H-X, Zhang R, Xia S-M, Rits-Volloch S, Sun L, Harrison SC, Haynes BF, Chen B. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20234–20239.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 1, 2009

Volume

106

Issue

48

Start / End Page

20234 / 20239

Location

United States

Related Subject Headings

  • Viral Vaccines
  • Protein Binding
  • Neutralization Tests
  • Mutation
  • Models, Molecular
  • Membranes, Artificial
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp41