Host glycocalyx captures HIV proximal to the cell surface via oligomannose-GlcNAc glycan-glycan interactions to support viral entry

  • Cell Rep. 2022 Feb 1;38(5):110296. doi: 10.1016/j.celrep.2022.110296.
Belinda L Spillings  1 ,  Christopher J Day  1 ,  Albert Garcia-Minambres  2 ,  Anupriya Aggarwal  3 ,  Nicholas D Condon  4 ,  Thomas Haselhorst  1 ,  Damian F J Purcell  5 ,  Stuart G Turville  3 ,  Jennifer L Stow  4 ,  Michael P Jennings  6 ,  Johnson Mak  7
Affiliations
  • 1. Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
  • 2. School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
  • 3. The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
  • 4. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
  • 5. The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • 6. Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia. Electronic address: [email protected].
  • 7. Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia; School of Medicine, Deakin University, Geelong, VIC 3216, Australia. Electronic address: [email protected].
PMID: 35108536 DOI: 10.1016/j.celrep.2022.110296
Abstract

Here, we present ultrastructural analyses showing that incoming HIV are captured near the lymphocyte surface in a virion-glycan-dependent manner. Biophysical analyses show that removal of either virion- or cell-associated N-glycans impairs virus-cell binding, and a similar glycan-dependent relationship is observed between purified HIV envelope (Env) and primary T cells. Trimming of N-glycans from either HIV or Env does not inhibit protein-protein interactions. Glycan arrays reveal HIV preferentially binds to N-acetylglucosamine and mannose. Interfering with these glycan-based interactions reduces HIV infectivity. These glycan interactions are distinct from previously reported glycan-lectin and non-specific electrostatic charge-based interactions. Specific glycan-glycan-mediated attachment occurs prior to virus entry and enhances efficiency of Infection. Binding and fluorescent imaging data support glycan-glycan interactions as being responsible, at least in part, for initiating contact between HIV and the host cell, prior to viral Env-cellular CD4 engagement.

Keywords
HIV; adhesion; attachment; glycan-glycan interaction; glycocalyx; non-electrostatic; virus entry.
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