Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants

Autores
High, Monica; Cho, Hye Youn; Marzec, Jacqui; Wiltshire, Tim; Verhein, Kirsten C.; Caballero, Mauricio Tomás; Acosta, Patricio Leandro; Ciencewicki, Jonathan; McCaw, Zackary R.; Kobzik, Lester; Miller DeGraff, Laura; Gladwell, Wes; Peden, David B.; Serra, M. Elina; Shi, Min; Weinberg, Clarice; Suzuki, Oscar; Wang, Xuting; Bell, Douglas A.; Polack, Fernando Pedro; Kleeberger, Steven R.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanismsremain unclear.Methods: We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5 days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates.Findings: GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV.Interpretation: Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies).
Fil: High, Monica. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Cho, Hye Youn. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Marzec, Jacqui. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Wiltshire, Tim. University of North Carolina; Estados Unidos
Fil: Verhein, Kirsten C.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ciencewicki, Jonathan. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: McCaw, Zackary R.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Kobzik, Lester. Harvard University. Harvard School of Public Health; Estados Unidos
Fil: Miller DeGraff, Laura. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Gladwell, Wes. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Peden, David B.. University Of North Carolina At Chapel Hill; Estados Unidos
Fil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Shi, Min. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Weinberg, Clarice. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Suzuki, Oscar. University of North Carolina; Estados Unidos
Fil: Wang, Xuting. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Bell, Douglas A.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados Unidos
Materia
INFECTIOUS DISEASE
INNATE IMMUNITY
LUNG
SNP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/116124
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/116124
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infantsHigh, MonicaCho, Hye YounMarzec, JacquiWiltshire, TimVerhein, Kirsten C.Caballero, Mauricio TomásAcosta, Patricio LeandroCiencewicki, JonathanMcCaw, Zackary R.Kobzik, LesterMiller DeGraff, LauraGladwell, WesPeden, David B.Serra, M. ElinaShi, MinWeinberg, ClariceSuzuki, OscarWang, XutingBell, Douglas A.Polack, Fernando PedroKleeberger, Steven R.INFECTIOUS DISEASEINNATE IMMUNITYLUNGSNPhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanismsremain unclear.Methods: We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5 days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates.Findings: GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV.Interpretation: Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies).Fil: High, Monica. National Institute Of Environmental Health Sciences; Estados UnidosFil: Cho, Hye Youn. National Institute Of Environmental Health Sciences; Estados UnidosFil: Marzec, Jacqui. National Institute Of Environmental Health Sciences; Estados UnidosFil: Wiltshire, Tim. University of North Carolina; Estados UnidosFil: Verhein, Kirsten C.. National Institute Of Environmental Health Sciences; Estados UnidosFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ciencewicki, Jonathan. National Institute Of Environmental Health Sciences; Estados UnidosFil: McCaw, Zackary R.. National Institute Of Environmental Health Sciences; Estados UnidosFil: Kobzik, Lester. Harvard University. Harvard School of Public Health; Estados UnidosFil: Miller DeGraff, Laura. National Institute Of Environmental Health Sciences; Estados UnidosFil: Gladwell, Wes. National Institute Of Environmental Health Sciences; Estados UnidosFil: Peden, David B.. University Of North Carolina At Chapel Hill; Estados UnidosFil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Shi, Min. National Institute Of Environmental Health Sciences; Estados UnidosFil: Weinberg, Clarice. National Institute Of Environmental Health Sciences; Estados UnidosFil: Suzuki, Oscar. University of North Carolina; Estados UnidosFil: Wang, Xuting. National Institute Of Environmental Health Sciences; Estados UnidosFil: Bell, Douglas A.. National Institute Of Environmental Health Sciences; Estados UnidosFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados UnidosElsevier2016-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/116124High, Monica; Cho, Hye Youn; Marzec, Jacqui; Wiltshire, Tim; Verhein, Kirsten C.; et al.; Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants; Elsevier; EBioMedicine; 11; 9-2016; 73-842352-39642352-3964CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2352396416303607info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2016.08.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:31:25Zoai:ri.conicet.gov.ar:11336/116124instacron: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:34982025-10-22 11:31:26.125CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
title Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
spellingShingle Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
High, Monica
INFECTIOUS DISEASE
INNATE IMMUNITY
LUNG
SNP
title_short Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
title_full Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
title_fullStr Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
title_full_unstemmed Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
title_sort Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants
dc.creator.none.fl_str_mv High, Monica
Cho, Hye Youn
Marzec, Jacqui
Wiltshire, Tim
Verhein, Kirsten C.
Caballero, Mauricio Tomás
Acosta, Patricio Leandro
Ciencewicki, Jonathan
McCaw, Zackary R.
Kobzik, Lester
Miller DeGraff, Laura
Gladwell, Wes
Peden, David B.
Serra, M. Elina
Shi, Min
Weinberg, Clarice
Suzuki, Oscar
Wang, Xuting
Bell, Douglas A.
Polack, Fernando Pedro
Kleeberger, Steven R.
author High, Monica
author_facet High, Monica
Cho, Hye Youn
Marzec, Jacqui
Wiltshire, Tim
Verhein, Kirsten C.
Caballero, Mauricio Tomás
Acosta, Patricio Leandro
Ciencewicki, Jonathan
McCaw, Zackary R.
Kobzik, Lester
Miller DeGraff, Laura
Gladwell, Wes
Peden, David B.
Serra, M. Elina
Shi, Min
Weinberg, Clarice
Suzuki, Oscar
Wang, Xuting
Bell, Douglas A.
Polack, Fernando Pedro
Kleeberger, Steven R.
author_role author
author2 Cho, Hye Youn
Marzec, Jacqui
Wiltshire, Tim
Verhein, Kirsten C.
Caballero, Mauricio Tomás
Acosta, Patricio Leandro
Ciencewicki, Jonathan
McCaw, Zackary R.
Kobzik, Lester
Miller DeGraff, Laura
Gladwell, Wes
Peden, David B.
Serra, M. Elina
Shi, Min
Weinberg, Clarice
Suzuki, Oscar
Wang, Xuting
Bell, Douglas A.
Polack, Fernando Pedro
Kleeberger, Steven R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv INFECTIOUS DISEASE
INNATE IMMUNITY
LUNG
SNP
topic INFECTIOUS DISEASE
INNATE IMMUNITY
LUNG
SNP
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanismsremain unclear.Methods: We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5 days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates.Findings: GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV.Interpretation: Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies).
Fil: High, Monica. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Cho, Hye Youn. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Marzec, Jacqui. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Wiltshire, Tim. University of North Carolina; Estados Unidos
Fil: Verhein, Kirsten C.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ciencewicki, Jonathan. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: McCaw, Zackary R.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Kobzik, Lester. Harvard University. Harvard School of Public Health; Estados Unidos
Fil: Miller DeGraff, Laura. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Gladwell, Wes. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Peden, David B.. University Of North Carolina At Chapel Hill; Estados Unidos
Fil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Shi, Min. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Weinberg, Clarice. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Suzuki, Oscar. University of North Carolina; Estados Unidos
Fil: Wang, Xuting. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Bell, Douglas A.. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados Unidos
description Background: Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanismsremain unclear.Methods: We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5 days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates.Findings: GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV.Interpretation: Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies).
publishDate 2016
dc.date.none.fl_str_mv 2016-09
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/11336/116124
High, Monica; Cho, Hye Youn; Marzec, Jacqui; Wiltshire, Tim; Verhein, Kirsten C.; et al.; Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants; Elsevier; EBioMedicine; 11; 9-2016; 73-84
2352-3964
2352-3964
CONICET Digital
CONICET
url http://hdl.handle.net/11336/116124
identifier_str_mv High, Monica; Cho, Hye Youn; Marzec, Jacqui; Wiltshire, Tim; Verhein, Kirsten C.; et al.; Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants; Elsevier; EBioMedicine; 11; 9-2016; 73-84
2352-3964
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://www.sciencedirect.com/science/article/pii/S2352396416303607
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2016.08.011
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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score 12.982451

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