Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor.
The primary event in the infection of cells by HIV is the interaction between the viral envelope glycoprotein, gp120, and its cellular receptor, CD4. A recombinant form of gp120 was found to bind to a recombinant CD4 antigen with high affinity. Two gp120-specific murine monoclonal antibodies were able to block the interaction between gp120 and CD4. The gp120 epitope of one of these antibodies was isolated by immunoaffinity chromatography of acid-cleaved gp120 and shown to be contained within amino acids 397-439. Using in vitro mutagenesis, we have found that deletion of 12 amino acids from this region of gp120 leads to a complete loss of binding. In addition, a single amino acid substitution in this region results in significantly decreased binding, suggesting that sequences within this region are directly involved in the binding of gp120 to the CD4 receptor.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000378:metabolism*; D017977:Deltaretrovirus / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120; D006801:Humans; D007157:Immunologic Surveillance; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus; D011994:Recombinant Proteins; D012191:Retroviridae Proteins