Details

Autor(en) / Beteiligte

• Woods, Christopher W
• McClain, Micah T
• Chen, Minhua
• Zaas, Aimee K
• Nicholson, Bradly P
• Varkey, Jay
• Veldman, Timothy
• Kingsmore, Stephen F
• Huang, Yongsheng
• Lambkin-Williams, Robert
• Gilbert, Anthony G
• Hero, 3rd, Alfred O
• Ramsburg, Elizabeth
• Glickman, Seth
• Lucas, Joseph E
• Carin, Lawrence
• Ginsburg, Geoffrey S
• Tse, Herman

Titel

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2

Ist Teil von

• PloS one, 2013-01, Vol.8 (1), p.e52198-e52198

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent.