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Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

dc.contributor.author Carin, Lawrence
dc.contributor.author Dobigeon, N
dc.contributor.author Ginsburg, Geoffrey Steven
dc.contributor.author Hero, Alfred
dc.contributor.author Huang, Y
dc.contributor.author Kingsmore, Stephen F
dc.contributor.author McClain, MT
dc.contributor.author Nicholson, B
dc.contributor.author Øien, NC
dc.contributor.author Rao, A
dc.contributor.author Varkey, JB
dc.contributor.author Veldman, T
dc.contributor.author Woods, Christopher Wildrick
dc.contributor.author Woolf, PJ
dc.contributor.author Zaas, Aimee Kirsch
dc.coverage.spatial United States
dc.date.accessioned 2014-07-22T16:11:07Z
dc.date.issued 2011-08
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21901105
dc.identifier PGENETICS-D-11-00033
dc.identifier.uri https://hdl.handle.net/10161/8945
dc.description.abstract Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.
dc.language eng
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1002234
dc.subject Adolescent
dc.subject Adult
dc.subject Asymptomatic Infections
dc.subject Cytokines
dc.subject Gene Expression Profiling
dc.subject Host-Pathogen Interactions
dc.subject Humans
dc.subject Influenza A Virus, H3N2 Subtype
dc.subject Influenza, Human
dc.subject Middle Aged
dc.subject Oxidative Stress
dc.subject Ribosomal Proteins
dc.subject Stress, Physiological
dc.title Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21901105
pubs.begin-page e1002234
pubs.issue 8
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Electrical and Computer Engineering
pubs.organisational-group Global Health Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 7
dc.identifier.eissn 1553-7404


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