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

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

Schork, Nicholas J

United States

2014-07-22T16:11:07Z

2011-08

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.

http://www.ncbi.nlm.nih.gov/pubmed/21901105

PGENETICS-D-11-00033

1553-7404

https://hdl.handle.net/10161/8945

eng

Public Library of Science (PLoS)

PLoS Genet

10.1371/journal.pgen.1002234

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

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

Journal article

Woods, Christopher W|0000-0001-7240-2453

Ginsburg, Geoffrey S|0000-0003-4739-9808

http://www.ncbi.nlm.nih.gov/pubmed/21901105

e1002234

8

Basic Science Departments

Biomedical Engineering

Clinical Science Departments

Duke

Duke Cancer Institute

Electrical and Computer Engineering

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

Pathology

Pratt School of Engineering

School of Medicine

School of Nursing

School of Nursing - Secondary Group

University Institutes and Centers

Published

7