title: 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.
authors: Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Yongsheng
authors: Y
authors: Huang
authors: Aimee K
authors: AK
authors: Zaas
authors: Arvind
authors: A
authors: Rao
authors: Nicolas
authors: N
authors: Dobigeon
authors: Peter J
authors: PJ
authors: Woolf
authors: Timothy
authors: T
authors: Veldman
authors: N Christine
authors: NC
authors: Øien
authors: Micah T
authors: MT
authors: McClain
authors: Jay B
authors: JB
authors: Varkey
authors: Bradley
authors: B
authors: Nicholson
authors: Lawrence
authors: L
authors: Carin
authors: Stephen
authors: S
authors: Kingsmore
authors: Christopher W
authors: CW
authors: Woods
authors: Geoffrey S
authors: GS
authors: Ginsburg
authors: Alfred O
authors: AO
authors: Hero
mesh_terms: D000293:Adolescent; D000328:Adult; D058345:Asymptomatic Infections; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D016207:Cytokines; D012269:Ribosomal Proteins