Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains

Shi Hua Xiang, Liping Wang, Mariam Abreu, Chih Chin Huang, Peter D. Kwong, Eric Rosenberg, James E. Robinson, Joseph Sodroski

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the β19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalVirology
Volume315
Issue number1
DOIs
StatePublished - Oct 10 2003

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Epitope Mapping
HIV-1
Monoclonal Antibodies
Antibodies
Chemokine Receptors
Glycoproteins

Keywords

  • CD4-induced (CD4i) antibodies
  • Envelope glycoprotein (gp120)
  • Epitope mapping
  • Human immunodeficiency virus (HIV-1)
  • Human monoclonal antibody E51
  • Neutralizing antibodies
  • Primary HIV-1 isolates
  • Soluble CD4 (sCD4)
  • Structured treatment interruption (STI)

ASJC Scopus subject areas

  • Virology

Cite this

Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains. / Xiang, Shi Hua; Wang, Liping; Abreu, Mariam; Huang, Chih Chin; Kwong, Peter D.; Rosenberg, Eric; Robinson, James E.; Sodroski, Joseph.

In: Virology, Vol. 315, No. 1, 10.10.2003, p. 124-134.

Research output: Contribution to journalArticle

Xiang, Shi Hua ; Wang, Liping ; Abreu, Mariam ; Huang, Chih Chin ; Kwong, Peter D. ; Rosenberg, Eric ; Robinson, James E. ; Sodroski, Joseph. / Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains. In: Virology. 2003 ; Vol. 315, No. 1. pp. 124-134.
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