title: Antibody neutralization and escape by HIV-1.
abstract: Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.
authors.affiliation: Howard Hughes Medical Institute, University of Alabama at Birmingham, 720 South 20th Street, KAUL 816, Birmingham, Alabama 35294-0024, USA.
authors.forename: Xiping
authors.initials: X
authors.lastname: Wei
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Shuyi
authors.initials: S
authors.lastname: Wang
authors.forename: Huxiong
authors.initials: H
authors.lastname: Hui
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wu
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilby
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Komarova
authors.forename: Martin A
authors.initials: MA
authors.lastname: Nowak
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009500:Neutralization Tests; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007106:Immune Sera