title: Quaternary epitope specificities of anti-HIV-1 neutralizing antibodies generated in rhesus macaques infected by the simian/human immunodeficiency virus SHIVSF162P4.
abstract: Monoclonal antibodies (MAbs) that neutralize human immunodeficiency virus type 1 (HIV-1) have been isolated from HIV-1-infected individuals or animals immunized with recombinant HIV-1 envelope (Env) glycoprotein constructs. The epitopes of these neutralizing antibodies (NAbs) were shown to be located on either the variable or conserved regions of the HIV-1 Env and to be linear or conformational. However, one neutralizing MAb, 2909, which was isolated from an HIV-1-infected subject, recognizes a more complex, quaternary epitope that is present on the virion-associated functional trimeric Env spike of the SF162 HIV-1 isolate. Here, we discuss the isolation of 11 anti-HIV NAbs that were isolated from three rhesus macaques infected with the simian/human immunodeficiency virus SHIV(SF162P4) and that also recognize quaternary epitopes. A detailed epitope mapping analysis of three of these rhesus antibodies revealed that their epitopes overlap that of the human MAb 2909. Despite this overall similarity in binding, however, differences in specific amino acid and glycosylation pattern requirements for MAb 2909 and the rhesus MAbs were identified. These results highlight similarities in the B-cell responses of humans and macaques to structurally complex neutralization epitopes on related viruses, HIV-1 and SHIV.
authors.affiliation: Department of Pediatrics, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70012, USA. jrobinso@tulane.edu
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.forename: Kelly
authors.initials: K
authors.lastname: Franco
authors.forename: Debra Holton
authors.initials: DH
authors.lastname: Elliott
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Maher
authors.forename: Ashley
authors.initials: A
authors.lastname: Reyna
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Zane
authors.initials: Z
authors.lastname: Kraft
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stamatatos
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000939:Epitopes; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D014771:Virion / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1