title: HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds.
abstract: BACKGROUND
  Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design.
  
  
  RESULTS
  Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection. The NAb response was dependent on the N332-glycan and viral resistance against the N332-glycan dependent bNAb PGT135 developed over time but viral escape did not occur at or near this glycan. In contrast, the virus likely escaped by increasing V1 length, with up to 21 amino acids, accompanied by the introduction of 1-3 additional glycans, as well as 2-4 additional cysteine residues within V1.
  
  
  CONCLUSIONS
  In the individual studied here, HIV-1 escaped from N332-glycan directed NAb responses without changing the epitope itself, but by elongating a variable loop that shields this epitope.
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Tom L G M
authors.initials: TL
authors.lastname: van den Kerkhof
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Steven W
authors.initials: SW
authors.lastname: de Taeye
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Brigitte D
authors.initials: BD
authors.lastname: Boeser-Nunnink
authors.affiliation: Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Janssen Pharmaceuticals, 2333 CN, Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands. r.w.sanders@amc.uva.nl.|Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY, 10065, USA. r.w.sanders@amc.uva.nl.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY, 10065, USA. m.j.vangils@amc.uva.nl.
authors.forename: Marit J
authors.initials: MJ
authors.lastname: van Gils
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D003545:Cysteine; D004220:Disulfides; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D008297:Male; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D004220:Disulfides; D015483:HIV Antibodies; D011134:Polysaccharides; D054299:env Gene Products, Human Immunodeficiency Virus; D003545:Cysteine
keywords: Broadly neutralizing antibodies; Cysteines; Envelope glycoprotein; Glycans; HIV-1; N332; Variable regions