A novel genetic locus linked to pro-inflammatory cytokines after virulent H5N1 virus infection in mice

Genetic variation in the human population is a key determinant of influenza disease severity. A single nucleotide polymorphism in the antiviral gene IFITM3 was linked to outcomes during the 2009 H1N1 pandemic. To identify variant host genes associated with increased virus replication and severe dise...

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Bibliographic Details
Published in:BMC genomics 2014-11, Vol.15 (1), p.1017-1017
Main Authors: Boon, Adrianus C M, Williams, Robert W, Sinasac, David S, Webby, Richard J
Format: Article
Language:English
Subjects:
Animals
Antiviral agents
Avian flu
Collagen - genetics
Cytokines
Cytokines - metabolism
Female
Genes
Genetic aspects
Genetic Association Studies
Genetic Linkage
Genomics
Health aspects
Hospitalization
Hospitals
Immune system
Infections
Infectious diseases
Inflammation Mediators - metabolism
Influenza A Virus, H5N1 Subtype
Influenza virus
Lungs
Medical research
Mice
Mice, Knockout
Mortality
Mutation, Missense
Neurosciences
Orthomyxoviridae Infections - genetics
Orthomyxoviridae Infections - metabolism
Orthomyxoviridae Infections - virology
Pathogenesis
Polymorphism, Genetic
Quantitative Trait Loci
Rodents
Species Specificity
Statistical analysis
Studies
Tumor Suppressor Proteins - genetics
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Summary:Genetic variation in the human population is a key determinant of influenza disease severity. A single nucleotide polymorphism in the antiviral gene IFITM3 was linked to outcomes during the 2009 H1N1 pandemic. To identify variant host genes associated with increased virus replication and severe disease, we performed a quantitative trait locus analysis on pro-inflammatory cytokine production 48 hours after intranasal infection with highly pathogenic H5N1 influenza virus. Pro-inflammatory cytokines CCL2, TNFα and IFN-α, were measured by ELISA in lung homogenates of DBA/2J (D2), C57BL/6J (B6) and 44 different BXD recombinant inbred mouse strains. Virus titer was also assessed in a subset of these animals. CCL2 (8-fold), TNFα (24-fold) and IFN-α (8-fold) concentrations varied significantly among the different BXD RI strains. Importantly, cytokine concentration correlated very well (r =0.86-0.96, P
ISSN:1471-2164
1471-2164
DOI:10.1186/1471-2164-15-1017