CD4-IgG binding threshold for inactivation of human immunodeficiency virus type 1.
The stoichiometry of human immunodeficiency virus type 1 (HIV-1) inactivation by soluble receptor CD4-IgG hybrid dimers (CD4-IgG) was examined. The extent of HIV-1 inactivation was measured in a sensitive plaque-forming assay, and the corresponding level of CD4-IgG binding was determined by immunofluorescence of infected cells. Ninety percent virus inactivation occurred at relatively low levels of CD4-IgG binding (10% of the saturating level). At even lower binding levels (1.4% of maximum binding), virus survival was 44%. Over a broad range of binding conditions, the survival curve followed a model in which viruses binding more than a threshold level of CD4-IgG were completely inactivated, while viruses binding less remained infectious. The data indicate that CD4-IgG binding to 1.4% of gp120 binding sites equals the threshold for inactivation. Thus, virus inactivation can begin when 3 CD4-IgG (of approximately 216 gp120 sites) bind per virion.
Berkower
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Laboratories of Immunoregulation, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland, USA.
Mostowski
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Bull
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Murphy
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D000937:Antigen-Antibody Reactions; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000737:chemistry* / Q000276:immunology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012995:Solubility; D010948:Viral Plaque Assay
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins