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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pgen.1002234

Publication Info

Huang, Yongsheng, Aimee K Zaas, Arvind Rao, Nicolas Dobigeon, Peter J Woolf, Timothy Veldman, N Christine Øien, Micah T McClain, et al. (2011). Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection. PLoS Genet, 7(8). p. 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.

Scholars@Duke

Zaas

Aimee Kirsch Zaas

Professor of Medicine

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

McClain

Micah Thomas McClain

Associate Professor of Medicine
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 Brooklyn Polytechnic Institute (now part of NYU) 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 2011-2014, and Vice Provost and Vice President for Research from 2014-2020. He was the Provost at King Abdullah University of Science & Technology (KAUST) from 2020-2023, returning to Duke in 2023. From 2003-2014 he held the William H. Younger Distinguished Professorship, and since 2018 he has held the James L. Meriam Distinguished Professorship. Dr. Carin's research focuses on machine learning (ML) and artificial intelligence (AI). He publishes widely in the main ML/AI forums, and has addressed many applications of AI, including in  medicine and security. He was co-founder of the small business Signal Innovations Group, which was acquired by BAE Systems in 2014, and in 2017 he co-founded the company Infinia ML, which was acquired by Aspirion in 2023. He is an IEEE Fellow.

Woods

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

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.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.