Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G

Guillaume B E Stewart-Jones; Cinque Soto; Thomas Lemmin; Gwo-Yu Chuang; Aliaksandr Druz; Rui Kong; Paul V Thomas; Kshitij Wagh; Tongqing Zhou; Anna-Janina Behrens; Tatsiana Bylund; Chang W Choi; Jack R Davison; Ivelin S Georgiev; M Gordon Joyce; Young Do Kwon; Marie Pancera; Justin Taft; Yongping Yang; Baoshan Zhang; Sachin S Shivatare; Vidya S Shivatare; Chang-Chun D Lee; Chung-Yi Wu; Carole A Bewley; Dennis R Burton; Wayne C Koff; Mark Connors; Max Crispin; Ulrich Baxa; Bette T Korber; Chi-Huey Wong; John R Mascola; Peter D Kwong

doi:10.1016/j.cell.2016.04.010

Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G

Cell. 2016 May 5;165(4):813-26. doi: 10.1016/j.cell.2016.04.010. Epub 2016 Apr 21.

Authors

Guillaume B E Stewart-Jones¹, Cinque Soto¹, Thomas Lemmin², Gwo-Yu Chuang¹, Aliaksandr Druz¹, Rui Kong¹, Paul V Thomas¹, Kshitij Wagh³, Tongqing Zhou¹, Anna-Janina Behrens⁴, Tatsiana Bylund¹, Chang W Choi¹, Jack R Davison⁵, Ivelin S Georgiev¹, M Gordon Joyce¹, Young Do Kwon¹, Marie Pancera¹, Justin Taft¹, Yongping Yang¹, Baoshan Zhang¹, Sachin S Shivatare⁶, Vidya S Shivatare⁶, Chang-Chun D Lee⁶, Chung-Yi Wu⁶, Carole A Bewley⁵, Dennis R Burton⁷, Wayne C Koff⁸, Mark Connors⁹, Max Crispin⁴, Ulrich Baxa¹⁰, Bette T Korber³, Chi-Huey Wong¹¹, John R Mascola¹, Peter D Kwong¹²

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA.
³ Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
⁴ Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
⁵ Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
⁷ Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, 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 International AIDS Vaccine Initiative, New York, NY 10038, USA.
⁹ HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁰ Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
¹¹ Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.

Abstract

The HIV-1-envelope (Env) trimer is covered by a glycan shield of ∼90 N-linked oligosaccharides, which comprises roughly half its mass and is a key component of HIV evasion from humoral immunity. To understand how antibodies can overcome the barriers imposed by the glycan shield, we crystallized fully glycosylated Env trimers from clades A, B, and G, visualizing the shield at 3.4-3.7 Å resolution. These structures reveal the HIV-1-glycan shield to comprise a network of interlocking oligosaccharides, substantially ordered by glycan crowding, that encase the protein component of Env and enable HIV-1 to avoid most antibody-mediated neutralization. The revealed features delineate a taxonomy of N-linked glycan-glycan interactions. Crowded and dispersed glycans are differently ordered, conserved, processed, and recognized by antibody. The structures, along with glycan-array binding and molecular dynamics, reveal a diversity in oligosaccharide affinity and a requirement for accommodating glycans among known broadly neutralizing antibodies that target the glycan-shielded trimer.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing / metabolism
Antibodies, Viral / metabolism
Crystallography, X-Ray
Glycosylation
HIV-1 / chemistry*
HIV-1 / classification
HIV-1 / immunology
Immune Evasion
Models, Molecular
Molecular Dynamics Simulation
Polysaccharides / analysis
Polysaccharides / metabolism
env Gene Products, Human Immunodeficiency Virus / chemistry*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Polysaccharides
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding