Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein
Anna-Janina Behrens,
Snezana Vasiljevic,
Laura K. Pritchard,
David J. Harvey,
Rajinder S. Andev,
Stefanie A. Krumm,
Weston B. Struwe,
Albert Cupo,
Abhinav Kumar,
Nicole Zitzmann,
Gemma E. Seabright,
Holger B. Kramer,
Daniel I.R. Spencer,
Louise Royle,
Jeong Hyun Lee,
Per J. Klasse,
Dennis R. Burton,
Ian A. Wilson,
Andrew B. Ward,
Rogier W. Sanders,
John P. Moore,
Katie J. Doores,
Max Crispin
Affiliations
Anna-Janina Behrens
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Snezana Vasiljevic
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Laura K. Pritchard
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
David J. Harvey
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Rajinder S. Andev
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK
Stefanie A. Krumm
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK
Weston B. Struwe
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Albert Cupo
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA
Abhinav Kumar
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Nicole Zitzmann
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Gemma E. Seabright
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Holger B. Kramer
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
Daniel I.R. Spencer
Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK
Louise Royle
Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK
Jeong Hyun Lee
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
Per J. Klasse
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA
Dennis R. Burton
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
Ian A. Wilson
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
Andrew B. Ward
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
Rogier W. Sanders
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA
John P. Moore
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA
Katie J. Doores
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK
Max Crispin
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
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.
