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Cell Rep. 2016 Mar 22;14(11):2695-706. doi: 10.1016/j.celrep.2016.02.058. Epub 2016 Mar 10.

Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein.

Author information

1
Oxford Glycobiology Institute and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
2
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK.
3
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
4
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
5
Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK.
6
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.
7
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.
8
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.
9
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.
10
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.
11
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.

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.

PMID:
26972002
PMCID:
PMC4805854
DOI:
10.1016/j.celrep.2016.02.058
[Indexed for MEDLINE]
Free PMC Article

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