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Glycan-mediated enhancement of reovirus receptor binding

Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multis...

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Autores principales: Koehler, Melanie, Aravamudhan, Pavithra, Guzman-Cardozo, Camila, Dumitru, Andra C., Yang, Jinsung, Gargiulo, Serena, Soumillion, Patrice, Dermody, Terence S., Alsteens, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773860/
https://www.ncbi.nlm.nih.gov/pubmed/31575869
http://dx.doi.org/10.1038/s41467-019-12411-2
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author Koehler, Melanie
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Dumitru, Andra C.
Yang, Jinsung
Gargiulo, Serena
Soumillion, Patrice
Dermody, Terence S.
Alsteens, David
author_facet Koehler, Melanie
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Dumitru, Andra C.
Yang, Jinsung
Gargiulo, Serena
Soumillion, Patrice
Dermody, Terence S.
Alsteens, David
author_sort Koehler, Melanie
collection PubMed
description Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents.
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spelling pubmed-67738602019-10-03 Glycan-mediated enhancement of reovirus receptor binding Koehler, Melanie Aravamudhan, Pavithra Guzman-Cardozo, Camila Dumitru, Andra C. Yang, Jinsung Gargiulo, Serena Soumillion, Patrice Dermody, Terence S. Alsteens, David Nat Commun Article Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents. Nature Publishing Group UK 2019-10-01 /pmc/articles/PMC6773860/ /pubmed/31575869 http://dx.doi.org/10.1038/s41467-019-12411-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Koehler, Melanie
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Dumitru, Andra C.
Yang, Jinsung
Gargiulo, Serena
Soumillion, Patrice
Dermody, Terence S.
Alsteens, David
Glycan-mediated enhancement of reovirus receptor binding
title Glycan-mediated enhancement of reovirus receptor binding
title_full Glycan-mediated enhancement of reovirus receptor binding
title_fullStr Glycan-mediated enhancement of reovirus receptor binding
title_full_unstemmed Glycan-mediated enhancement of reovirus receptor binding
title_short Glycan-mediated enhancement of reovirus receptor binding
title_sort glycan-mediated enhancement of reovirus receptor binding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773860/
https://www.ncbi.nlm.nih.gov/pubmed/31575869
http://dx.doi.org/10.1038/s41467-019-12411-2
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