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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/144365

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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