Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies

Qing Wei; Audra A. Hargett; Barbora Knoppova; Alexandra Duverger; Reda Rawi; Chen-Hsiang Shen; S. Katie Farney; Stacy Hall; Rhubell Brown; Brandon F. Keele; Sonya L. Heath; Michael S. Saag; Olaf Kutsch; Gwo-Yu Chuang; Peter D. Kwong; Zina Moldoveanu; Milan Raska; Matthew B. Renfrow; Jan Novak

iScience (Nov 2020)

Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies

Qing Wei,
Audra A. Hargett,
Barbora Knoppova,
Alexandra Duverger,
Reda Rawi,
Chen-Hsiang Shen,
S. Katie Farney,
Stacy Hall,
Rhubell Brown,
Brandon F. Keele,
Sonya L. Heath,
Michael S. Saag,
Olaf Kutsch,
Gwo-Yu Chuang,
Peter D. Kwong,
Zina Moldoveanu,
Milan Raska,
Matthew B. Renfrow,
Jan Novak

Affiliations

Qing Wei: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA
Audra A. Hargett: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
Barbora Knoppova: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA
Alexandra Duverger: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Reda Rawi: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Chen-Hsiang Shen: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
S. Katie Farney: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Stacy Hall: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA
Rhubell Brown: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA
Brandon F. Keele: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Sonya L. Heath: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Michael S. Saag: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Olaf Kutsch: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Gwo-Yu Chuang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Peter D. Kwong: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Zina Moldoveanu: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA
Milan Raska: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA; Department of Immunology, Palacky University Olomouc, Olomouc, Czech Republic
Matthew B. Renfrow: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding author
Jan Novak: Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 11
p. 101711

Abstract

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Summary: HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion. How each glycan interacts to shape the Env-protein-sugar complex and affects Env function is not well understood. Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization. Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing. Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss. This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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