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
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.
