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

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Date
2011-08
Authors
Huang, Yongsheng
Zaas, Aimee K
Rao, Arvind
Dobigeon, Nicolas
Woolf, Peter J
Veldman, Timothy
Øien, N Christine
McClain, Micah T
Varkey, Jay B
Nicholson, Bradley
Carin, Lawrence
Kingsmore, Stephen
Kingsmore, Stephen
Woods, Christopher W
Ginsburg, Geoffrey S
Hero, Alfred O
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(16 total)
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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.
Type
Journal article
Subject
Adolescent
Adult
Asymptomatic Infections
Cytokines
Gene Expression Profiling
Host-Pathogen Interactions
Humans
Influenza A Virus, H3N2 Subtype
Influenza, Human
Middle Aged
Oxidative Stress
Ribosomal Proteins
Stress, Physiological
Permalink
https://hdl.handle.net/10161/8945
Published Version (Please cite this version)
10.1371/journal.pgen.1002234
Publication Info
Huang, Yongsheng; Zaas, Aimee K; Rao, Arvind; Dobigeon, Nicolas; Woolf, Peter J; Veldman, Timothy; ... Hero, Alfred O (2011). Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection. PLoS Genet, 7(8). pp. e1002234. 10.1371/journal.pgen.1002234. Retrieved from https://hdl.handle.net/10161/8945.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Carin

Lawrence Carin

Professor of Electrical and Computer Engineering
Lawrence Carin earned the BS, MS, and PhD degrees in electrical engineering at the University of Maryland, College Park, in 1985, 1986, and 1989, respectively. In 1989 he joined the Electrical Engineering Department at Polytechnic University (Brooklyn) as an Assistant Professor, and became an Associate Professor there in 1994. In September 1995 he joined the Electrical and Computer Engineering (ECE) Department at Duke University, where he is now a Professor. He was ECE Department Chair from 2011
Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
McClain

Micah Thomas McClain

Associate Professor of Medicine
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
Zaas

Aimee Kirsch Zaas

Professor of Medicine
Medical education Genomic applications for diagnosis of infectious diseases Genomic applications for prediction of infectious diseases
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