title: Identification of gp120 regions targeted by a highly potent neutralizing antiserum elicited in a chimpanzee inoculated with a primary human immunodeficiency virus type 1 isolate.
abstract: We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an extremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred sterilizing immunity following passive transfer to macaques which were subsequently challenged with simian immunodeficiency virus/HIV-1 chimeric virus strain DH12. In addition to being highly strain specific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV-1(DH12), nor did it block the interaction of gp120 with the CD4 receptor. When neutralization was examined in the context of virus particles carrying chimeric envelope glycoproteins, the presence of all five hypervariable regions (V1 to V5) was required for optimal neutralization. Virions bearing chimeric gp120 containing the V1-V2 and V4 regions of HIV-1(DH12) could also be neutralized, but larger quantities of the chimpanzee antiserum were needed to block infection. These results indicate that the HIV-1 gp120 epitope(s) targeted by the chimpanzee antiserum is highly conformational, involving surface elements contributed by all of the hypervariable domains of the envelope glycoprotein.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mcho@nih.gov
authors.forename: M W
authors.initials: MW
authors.lastname: Cho
authors.forename: M K
authors.initials: MK
authors.lastname: Lee
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Matthews
authors.forename: M A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology*; D002679:Pan troglodytes; D019713:Receptors, CCR5 / Q000032:analysis
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D019713:Receptors, CCR5