Structural modulations of the envelope gp120 glycoprotein of human immunodeficiency virus type 1 upon oligomerization and differential V3 loop epitope exposure of isolates displaying distinct tropism upon virion-soluble receptor binding.
We investigated the binding of conformation-dependent anti-V2, anti-V3, and anti-CD4-binding site monoclonal antibodies to monomeric and virion-associated gp120 from human immunodeficiency virus type 1 isolates displaying marked differences in cell tropism. For all viruses examined, we found that the half-maximal binding values of the anti-V2 and anti-CD4-binding site antibodies with virion-associated gp120 were higher than those with monomeric gp120, but the maximum amount of antibodies bound was diminished only for one of the anti-V2 antibodies tested. These observations suggest that upon gp120 oligomerization, the V2 loop and CD4-binding site undergo conformational changes and that particular epitopes within these domains are occluded in the oligomeric gp120. In contrast, although the overall binding patterns and half-maximal binding values of the anti-V3 loop antibodies tested were similar with monomeric and oligomeric gp120, all the V3 loop epitopes examined were less accessible to antibody binding on the virion surface. This masking of the V3 loop is more pronounced for the primary-like macrophage-tropic isolates examined. Lastly, we observe that upon soluble receptor-virion binding, specific V3 loop epitopes that differ for viruses displaying different tropisms are exposed.
Stamatatos
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L
Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016, USA.
Cheng-Mayer
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C
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014771:Virion / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120