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Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

Huang, Yongsheng and Zaas, Aimee K. and Rao, Arvind and Dobigeon, Nicolas and Woolf, Peter J. and Veldman, Timothy and Oien, N. Christine and McClain, Micah T. and Varkey, Jay B. and Nicholson, Bradley and Carin, Lawrence and Kingsmore, Stephen and Woods, Christopher W. and Ginsburg, Geoffrey S. and Hero, Alfred O. Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection. (2011) PLoS Genetics, vol. 7 (n° 8). pp.1-17. ISSN 1553-7390

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Official URL: http://dx.doi.org/10.1371/journal.pgen.1002234

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.

Item Type:Article
Additional Information:Thanks to Public Library of Science. The definitive version is available at http://www.plos.org/ The original PDF of the article can be found at PLoS Genetics website : http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002234
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS
Other partners > Carnegie Mellon University - CMU (USA)
Other partners > Children’s Mercy Hospital (USA)
Other partners > Duke University (USA)
Other partners > Emory University (USA)
Université de Toulouse > Institut National Polytechnique de Toulouse - INPT
Université de Toulouse > Université Paul Sabatier-Toulouse III - UPS
Université de Toulouse > Université de Toulouse II-Le Mirail - UTM
Université de Toulouse > Université de Toulouse I-Sciences Sociales - UT1
Other partners > University of Michigan - U-M (USA)
Laboratory name:
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Deposited By:Nicolas DOBIGEON

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