title: Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein.
abstract: The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Anna-Janina
authors.initials: AJ
authors.lastname: Behrens
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Snezana
authors.initials: S
authors.lastname: Vasiljevic
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Pritchard
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.affiliation: Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Rajinder S
authors.initials: RS
authors.lastname: Andev
authors.affiliation: Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Krumm
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Weston B
authors.initials: WB
authors.lastname: Struwe
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Cupo
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Zitzmann
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Gemma E
authors.initials: GE
authors.lastname: Seabright
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Holger B
authors.initials: HB
authors.lastname: Kramer
authors.affiliation: Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK.
authors.forename: Daniel I R
authors.initials: DI
authors.lastname: Spencer
authors.affiliation: Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.affiliation: Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and CAVD, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Per J
authors.initials: PJ
authors.lastname: Klasse
authors.affiliation: Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center and CAVD, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, the Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02142, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and CAVD, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and CAVD, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA; Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.affiliation: Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK. Electronic address: katie.doores@kcl.ac.uk.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Doores
authors.affiliation: Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: max.crispin@bioch.ox.ac.uk.
authors.forename: Max
authors.initials: M
authors.lastname: Crispin
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D006020:Glycopeptides / Q000032:analysis; D006031:Glycosylation; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D011134:Polysaccharides / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D057134:Antibodies, Neutralizing; D006020:Glycopeptides; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; D011994:Recombinant Proteins