title: Antigenic variation within the CD4 binding site of human immunodeficiency virus type 1 gp120: effects on chemokine receptor utilization.
abstract: To assess the antigenicity of envelope glycoproteins derived from primary human immunodeficiency virus type 1 populations, their interactions with the receptor CD4, and their coreceptor usage, we have cloned and expressed multiple gp120 proteins from a number of primary virus isolates. Characterization of these proteins showed a high degree of antigenic polymorphism both within the CD4 binding site and in defined neutralization epitopes, which may partially account for the general resistance of primary isolates to neutralizing agents. Furthermore, chimeric viruses expressing gp120 proteins with reduced CD4 binding abilities are viable, suggesting that primary viruses may require a less avid interaction with the receptor CD4 to initiate infection than do their laboratory-adapted counterparts. The coreceptor usage of chimeric viruses was related to the ability of the virus to bind CD4, with reduced CD4 binding correlating with preferential usage of CXCR4. Changes in coreceptor usage mapped to sequence changes in the C2 and V4 regions, with no changes seen in the V3 region.
authors.affiliation: School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 2AJ, United Kingdom. murphy.anthea@mayo.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Hammond
authors.forename: J
authors.initials: J
authors.lastname: Lewis
authors.forename: J
authors.initials: J
authors.lastname: May
authors.forename: J
authors.initials: J
authors.lastname: Albert
authors.forename: P
authors.initials: P
authors.lastname: Balfe
authors.forename: J A
authors.initials: JA
authors.lastname: McKeating
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D019707:Receptors, Chemokine / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins