title: Both neutralization resistance and high infectivity phenotypes are caused by mutations of interacting residues in the human immunodeficiency virus type 1 gp41 leucine zipper and the gp120 receptor- and coreceptor-binding domains.
abstract: Neutralization resistance of human immunodeficiency virus type 1 (HIV-1) is a major impediment to vaccine development. We have found that residues of HIV-1 MN strain in the C terminus of gp120 and the leucine zipper (LZ) region of gp41 viral envelope proteins interact cooperatively to determine neutralization resistance and modulate infectivity. Further, results demonstrate that this interaction, by which regions of gp120 are assembled onto the LZ, involves amino acid residues intimately related to those which participate in the binding of the envelope to its receptor and coreceptor. Variations in this critical assembly structure determine the concordant, interdependent evolution of increased infectivity efficiency and neutralization resistance phenotypes of the envelopes. The results elucidate important structure-function relationships among epitopes that are important targets of vaccine development.
authors.affiliation: Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Park
authors.forename: G V
authors.initials: GV
authors.lastname: Quinnan
mesh_terms: D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019718:Receptors, CXCR4