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PLoS Genet. 2011 Aug;7(8):e1002234. doi: 10.1371/journal.pgen.1002234. Epub 2011 Aug 25.

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

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1
Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America.

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.

PMID:
21901105
PMCID:
PMC3161909
DOI:
10.1371/journal.pgen.1002234
[Indexed for MEDLINE]
Free PMC Article
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