tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2020 May 26;201921962.
doi: 10.1073/pnas.1921962117. Online ahead of print.
Membrane-tethered Mucin-Like Polypeptides Sterically Inhibit Binding and Slow Fusion Kinetics of Influenza A Virus
Corleone S Delaveris[SUP] 1 [/SUP], Elizabeth R Webster[SUP] 1 [/SUP], Steven M Banik[SUP] 1 [/SUP], Steven G Boxer[SUP] 2 [/SUP], Carolyn R Bertozzi[SUP] 2 3 [/SUP]
Affiliations
Abstract
The mechanism(s) by which cell-tethered mucins modulate infection by influenza A viruses (IAVs) remain an open question. Mucins form both a protective barrier that can block virus binding and recruit IAVs to bind cells via the sialic acids of cell-tethered mucins. To elucidate the molecular role of mucins in flu pathogenesis, we constructed a synthetic glycocalyx to investigate membrane-tethered mucins in the context of IAV binding and fusion. We designed and synthesized lipid-tethered glycopolypeptide mimics of mucins and added them to lipid bilayers, allowing chemical control of length, glycosylation, and surface density of a model glycocalyx. We observed that the mucin mimics undergo a conformational change at high surface densities from a compact to an extended architecture. At high surface densities, asialo mucin mimics inhibited IAV binding to underlying glycolipid receptors, and this density correlated to the mucin mimic's conformational transition. Using a single virus fusion assay, we observed that while fusion of virions bound to vesicles coated with sialylated mucin mimics was possible, the kinetics of fusion was slowed in a mucin density-dependent manner. These data provide a molecular model for a protective mechanism by mucins in IAV infection, and therefore this synthetic glycocalyx provides a useful reductionist model for studying the complex interface of host-pathogen interactions.
Keywords: glycobiology; influenza A virus; mucin.
. 2020 May 26;201921962.
doi: 10.1073/pnas.1921962117. Online ahead of print.
Membrane-tethered Mucin-Like Polypeptides Sterically Inhibit Binding and Slow Fusion Kinetics of Influenza A Virus
Corleone S Delaveris[SUP] 1 [/SUP], Elizabeth R Webster[SUP] 1 [/SUP], Steven M Banik[SUP] 1 [/SUP], Steven G Boxer[SUP] 2 [/SUP], Carolyn R Bertozzi[SUP] 2 3 [/SUP]
Affiliations
- PMID: 32457151
- DOI: 10.1073/pnas.1921962117
Abstract
The mechanism(s) by which cell-tethered mucins modulate infection by influenza A viruses (IAVs) remain an open question. Mucins form both a protective barrier that can block virus binding and recruit IAVs to bind cells via the sialic acids of cell-tethered mucins. To elucidate the molecular role of mucins in flu pathogenesis, we constructed a synthetic glycocalyx to investigate membrane-tethered mucins in the context of IAV binding and fusion. We designed and synthesized lipid-tethered glycopolypeptide mimics of mucins and added them to lipid bilayers, allowing chemical control of length, glycosylation, and surface density of a model glycocalyx. We observed that the mucin mimics undergo a conformational change at high surface densities from a compact to an extended architecture. At high surface densities, asialo mucin mimics inhibited IAV binding to underlying glycolipid receptors, and this density correlated to the mucin mimic's conformational transition. Using a single virus fusion assay, we observed that while fusion of virions bound to vesicles coated with sialylated mucin mimics was possible, the kinetics of fusion was slowed in a mucin density-dependent manner. These data provide a molecular model for a protective mechanism by mucins in IAV infection, and therefore this synthetic glycocalyx provides a useful reductionist model for studying the complex interface of host-pathogen interactions.
Keywords: glycobiology; influenza A virus; mucin.