Hierarchical Multivalent Effects Control Influenza Host Specificity
- Autores
- Overeem, Nico J.; Hamming, P. H. Erik; Grant, Oliver C.; Di Iorio, Daniele; Tieke, Malte; Bertolino, María Candelaria; Li, Zeshi; Vos, Gaël; de Vries, Robert P.; Woods, Robert J.; Tito, Nicholas B.; Boons, Geert-Jan P. H.; van der Vries, Erhard; Huskens, Jurriaan
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential.
Fil: Overeem, Nico J.. University of Twente; Países Bajos
Fil: Hamming, P. H. Erik. University of Twente; Países Bajos
Fil: Grant, Oliver C.. University of Georgia; Estados Unidos
Fil: Di Iorio, Daniele. University of Twente; Países Bajos
Fil: Tieke, Malte. Utrecht University; Países Bajos
Fil: Bertolino, María Candelaria. University of Twente; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Li, Zeshi. Utrecht University; Países Bajos
Fil: Vos, Gaël. Utrecht University; Países Bajos
Fil: de Vries, Robert P.. Utrecht University; Países Bajos
Fil: Woods, Robert J.. University of Georgia; Estados Unidos
Fil: Tito, Nicholas B.. Electric Ant Laboratory; Países Bajos
Fil: Boons, Geert-Jan P. H.. Utrecht University; Países Bajos
Fil: van der Vries, Erhard. Utrecht University; Países Bajos
Fil: Huskens, Jurriaan. University of Twente; Países Bajos - Materia
-
Viruses
Chemical specificity
Carbohydrates
Receptors - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/144365
Ver los metadatos del registro completo
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Hierarchical Multivalent Effects Control Influenza Host SpecificityOvereem, Nico J.Hamming, P. H. ErikGrant, Oliver C.Di Iorio, DanieleTieke, MalteBertolino, María CandelariaLi, ZeshiVos, Gaëlde Vries, Robert P.Woods, Robert J.Tito, Nicholas B.Boons, Geert-Jan P. H.van der Vries, ErhardHuskens, JurriaanVirusesChemical specificityCarbohydratesReceptorshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential.Fil: Overeem, Nico J.. University of Twente; Países BajosFil: Hamming, P. H. Erik. University of Twente; Países BajosFil: Grant, Oliver C.. University of Georgia; Estados UnidosFil: Di Iorio, Daniele. University of Twente; Países BajosFil: Tieke, Malte. Utrecht University; Países BajosFil: Bertolino, María Candelaria. University of Twente; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Li, Zeshi. Utrecht University; Países BajosFil: Vos, Gaël. Utrecht University; Países BajosFil: de Vries, Robert P.. Utrecht University; Países BajosFil: Woods, Robert J.. University of Georgia; Estados UnidosFil: Tito, Nicholas B.. Electric Ant Laboratory; Países BajosFil: Boons, Geert-Jan P. H.. Utrecht University; Países BajosFil: van der Vries, Erhard. Utrecht University; Países BajosFil: Huskens, Jurriaan. University of Twente; Países BajosAmerican Chemical Society2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/144365Overeem, Nico J.; Hamming, P. H. Erik; Grant, Oliver C.; Di Iorio, Daniele; Tieke, Malte; et al.; Hierarchical Multivalent Effects Control Influenza Host Specificity; American Chemical Society; ACS Central Science; 6; 12; 11-2020; 1-82374-79432374-7951CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acscentsci.0c01175info:eu-repo/semantics/altIdentifier/doi/10.1021/acscentsci.0c01175info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:28Zoai:ri.conicet.gov.ar:11336/144365instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:48:28.821CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
title |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
spellingShingle |
Hierarchical Multivalent Effects Control Influenza Host Specificity Overeem, Nico J. Viruses Chemical specificity Carbohydrates Receptors |
title_short |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
title_full |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
title_fullStr |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
title_full_unstemmed |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
title_sort |
Hierarchical Multivalent Effects Control Influenza Host Specificity |
dc.creator.none.fl_str_mv |
Overeem, Nico J. Hamming, P. H. Erik Grant, Oliver C. Di Iorio, Daniele Tieke, Malte Bertolino, María Candelaria Li, Zeshi Vos, Gaël de Vries, Robert P. Woods, Robert J. Tito, Nicholas B. Boons, Geert-Jan P. H. van der Vries, Erhard Huskens, Jurriaan |
author |
Overeem, Nico J. |
author_facet |
Overeem, Nico J. Hamming, P. H. Erik Grant, Oliver C. Di Iorio, Daniele Tieke, Malte Bertolino, María Candelaria Li, Zeshi Vos, Gaël de Vries, Robert P. Woods, Robert J. Tito, Nicholas B. Boons, Geert-Jan P. H. van der Vries, Erhard Huskens, Jurriaan |
author_role |
author |
author2 |
Hamming, P. H. Erik Grant, Oliver C. Di Iorio, Daniele Tieke, Malte Bertolino, María Candelaria Li, Zeshi Vos, Gaël de Vries, Robert P. Woods, Robert J. Tito, Nicholas B. Boons, Geert-Jan P. H. van der Vries, Erhard Huskens, Jurriaan |
author2_role |
author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Viruses Chemical specificity Carbohydrates Receptors |
topic |
Viruses Chemical specificity Carbohydrates Receptors |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential. Fil: Overeem, Nico J.. University of Twente; Países Bajos Fil: Hamming, P. H. Erik. University of Twente; Países Bajos Fil: Grant, Oliver C.. University of Georgia; Estados Unidos Fil: Di Iorio, Daniele. University of Twente; Países Bajos Fil: Tieke, Malte. Utrecht University; Países Bajos Fil: Bertolino, María Candelaria. University of Twente; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Li, Zeshi. Utrecht University; Países Bajos Fil: Vos, Gaël. Utrecht University; Países Bajos Fil: de Vries, Robert P.. Utrecht University; Países Bajos Fil: Woods, Robert J.. University of Georgia; Estados Unidos Fil: Tito, Nicholas B.. Electric Ant Laboratory; Países Bajos Fil: Boons, Geert-Jan P. H.. Utrecht University; Países Bajos Fil: van der Vries, Erhard. Utrecht University; Países Bajos Fil: Huskens, Jurriaan. University of Twente; Países Bajos |
description |
Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/144365 Overeem, Nico J.; Hamming, P. H. Erik; Grant, Oliver C.; Di Iorio, Daniele; Tieke, Malte; et al.; Hierarchical Multivalent Effects Control Influenza Host Specificity; American Chemical Society; ACS Central Science; 6; 12; 11-2020; 1-8 2374-7943 2374-7951 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/144365 |
identifier_str_mv |
Overeem, Nico J.; Hamming, P. H. Erik; Grant, Oliver C.; Di Iorio, Daniele; Tieke, Malte; et al.; Hierarchical Multivalent Effects Control Influenza Host Specificity; American Chemical Society; ACS Central Science; 6; 12; 11-2020; 1-8 2374-7943 2374-7951 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acscentsci.0c01175 info:eu-repo/semantics/altIdentifier/doi/10.1021/acscentsci.0c01175 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |