Multifaceted consequences of anti-gp41 monoclonal antibody 2F5 binding to HIV type 1 virions.
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.
Neurath
A R
AR
Lindsley F. Kimball Research Institute, New York Blood Center, New York 10021, USA.
Strick
N
N
Lin
K
K
Jiang
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D014771:Virion / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments