Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
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 articleSubject
AdolescentAdult
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
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https://hdl.handle.net/10161/8945Published Version (Please cite this version)
10.1371/journal.pgen.1002234Publication 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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Show full item recordScholars@Duke
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
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.
Micah Thomas McClain
Associate Professor of Medicine
Christopher Wildrick Woods
Wolfgang Joklik Distinguished Professor of Global Health
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
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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