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dc.contributor.author
High, Monica
dc.contributor.author
Cho, Hye Youn
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Marzec, Jacqui
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Wiltshire, Tim
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Verhein, Kirsten C.
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Caballero, Mauricio Tomás
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Acosta, Patricio Leandro
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Ciencewicki, Jonathan
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McCaw, Zackary R.
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Kobzik, Lester
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Miller DeGraff, Laura
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Gladwell, Wes
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Peden, David B.
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Serra, M. Elina
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Shi, Min
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Weinberg, Clarice
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Suzuki, Oscar
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Wang, Xuting
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Bell, Douglas A.
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Polack, Fernando Pedro
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dc.contributor.author
Kleeberger, Steven R.
dc.date.available
2020-10-19T15:56:47Z
dc.date.issued
2016-09
dc.identifier.citation
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
dc.identifier.issn
2352-3964
dc.identifier.uri
http://hdl.handle.net/11336/116124
dc.description.abstract
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).
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
INFECTIOUS DISEASE
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INNATE IMMUNITY
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LUNG
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SNP
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.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
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-10-09T15:53:07Z
dc.identifier.eissn
2352-3964
dc.journal.volume
11
dc.journal.pagination
73-84
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: High, Monica. National Institute Of Environmental Health Sciences; Estados Unidos
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Fil: Cho, Hye Youn. National Institute Of Environmental Health Sciences; Estados Unidos
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Fil: Marzec, Jacqui. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Wiltshire, Tim. University of North Carolina; Estados Unidos
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Fil: Verhein, Kirsten C.. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Ciencewicki, Jonathan. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: McCaw, Zackary R.. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Kobzik, Lester. Harvard University. Harvard School of Public Health; Estados Unidos
dc.description.fil
Fil: Miller DeGraff, Laura. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Gladwell, Wes. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Peden, David B.. University Of North Carolina At Chapel Hill; Estados Unidos
dc.description.fil
Fil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; Argentina
dc.description.fil
Fil: Shi, Min. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Weinberg, Clarice. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Suzuki, Oscar. University of North Carolina; Estados Unidos
dc.description.fil
Fil: Wang, Xuting. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Bell, Douglas A.. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados Unidos
dc.journal.title
EBioMedicine
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2352396416303607
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ebiom.2016.08.011
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