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

doi:10.1016/j.isci.2020.101711

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

iScience. 2020 Oct 21;23(11):101711. doi: 10.1016/j.isci.2020.101711. eCollection 2020 Nov 20.

Authors

Qing Wei¹, Audra A Hargett², Barbora Knoppova¹, Alexandra Duverger³, Reda Rawi⁴, Chen-Hsiang Shen⁴, S Katie Farney⁴, Stacy Hall¹, Rhubell Brown¹, Brandon F Keele⁵, Sonya L Heath³, Michael S Saag³, Olaf Kutsch³, Gwo-Yu Chuang⁴, Peter D Kwong⁴, Zina Moldoveanu¹, Milan Raska^{1

6}, Matthew B Renfrow², Jan Novak¹

Affiliations

¹ Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA.
² Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
³ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁶ Department of Immunology, Palacky University Olomouc, Olomouc, Czech Republic.

Abstract

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.

Keywords: Biochemistry; Biological Sciences; Glycobiology; Microbiology; Virology.

Abstract

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