Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Multifaceted consequences of anti-gp41 monoclonal antibody 2F5 binding to HIV type 1 virions.
AIDS Res Hum Retroviruses. 1995 Jun;11(6):687-96. Unique Identifier : AIDSLINE MED/96078229 Neurath AR; Strick N; Lin K; Jiang S; Lindsley F. Kimball Research Institute, New York Blood Center,; New York 10021, USA.
Abstract:
A human monoclonal antibody (MAb) (2F5) neutralizing a variety of laboratory strains and clinical isolates of the human immunodeficiency virus type 1 (HIV-1) and binding to an epitope of the envelope glycoprotein gp41 encompassing the amino acid sequence ELDKWA has been described (Muster T et al., J Virol 1993;67:6642-6647). It was suggested that an immunogen eliciting virus-neutralizing antibodies having a specificity similar to that of MAb 2F5 should be considered as a component of HIV-1 vaccines. Efforts in this direction would benefit from understanding the mechanism whereby MAb 2F5 neutralizes the infectivity of HIV-1. The segment of gp41 encompassing residues ELDKWA has so far not been directly implicated in initiation of infection by HIV-1, suggesting that MAb 2F5 might affect other sites on HIV-1 envelope glycoproteins playing a role in virus entry into target cells. We provide here evidence that MAb 2F5 binding to HIV-1 virus particles decreases the accessibility or conformation of the gp41 fusion domain and of gp120 domains, including the binding site for the CD4 cell receptor. These apparently indirect consequences of MAb 2F5 binding to HIV-1 are likely to account for or contribute to the virus-neutralizing activity of this MAb.
Keywords: Amino Acid Sequence Antibodies, Monoclonal/*IMMUNOLOGY/METABOLISM Antigens, CD4/METABOLISM Binding Sites Cell Fusion Epitope Mapping HIV Antibodies/*IMMUNOLOGY/METABOLISM HIV Envelope Protein gp120/METABOLISM HIV Envelope Protein gp41/CHEMISTRY/GENETICS/*IMMUNOLOGY HIV-1/*IMMUNOLOGY Molecular Sequence Data Neutralization Tests Peptide Fragments/CHEMICAL SYNTHESIS/IMMUNOLOGY/METABOLISM Protein Conformation Sequence Alignment Support, U.S. Gov't, P.H.S. Virion/*IMMUNOLOGY JOURNAL ARTICLE 960228
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