title: Regions required for CD4 binding in the external glycoprotein gp120 of simian immunodeficiency virus.
abstract: The external domain of the envelope glycoprotein, gp120, of simian immunodeficiency virus (SIV) has been expressed as a mature secreted product using recombinant baculoviruses and the expressed protein, which has an observed molecular mass of 110 kDa, was purified by monoclonal antibody (MAb) affinity chromatography. N-terminal sequence analysis showed a signal sequence cleavage identity similar to that of the gp120s of both human immunodeficiency virus type 1 (HIV-1) and HIV type 2. The expressed molecule bound to soluble CD4 with an affinity that was approximately 10-fold lower than that of gp120 from HIV-1. A screening of the ability of SIV envelope MAbs to inhibit CD4 binding revealed two groups of inhibitory MAbs. One group is dependent on conformation, while the second group maps to a discrete epitope near the amino terminus. The particular role of the V3 loop region of the molecule in CD4 binding was investigated by the construction of an SIV-HIV hybrid in which the V3 loop of SIV was precisely replaced with the equivalent domain from HIV-1 MN. The hybrid glycoprotein bound HIV-1 V3 loop MAbs and not SIV V3 MAbs but continued to bind conformational SIV MAbs and soluble CD4 as well as the parent molecule.
authors: NERC Institute of Virology, Oxford United Kingdom.
authors: C B
authors: CB
authors: Doyle
authors: U
authors: U
authors: Bhattacharyya
authors: K A
authors: KA
authors: Kent
authors: J E
authors: JE
authors: Stott
authors: I M
authors: IM
authors: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014759:Viral Envelope Proteins
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus