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Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection
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نویسنده
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huang y. ,zaas a.k. ,rao a. ,dobigeon n. ,woolf p.j. ,veldman t. ,øien n.c. ,mcclain m.t. ,varkey j.b. ,nicholson b. ,carin l. ,kingsmore s. ,woods c.w. ,ginsburg g.s. ,hero a.o.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 8
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چکیده
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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. © 2011 huang et al.
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آدرس
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center for computational biology and bioinformatics,university of michigan,ann arbor,mi,united states,department of statistics,university of michigan,ann arbor,mi, United States, institute for genome sciences and policy,duke university,durham,nc,united states,department of medicine,duke university,durham,nc, United States, lane center for computational biology,carnegie mellon university,pittsburgh,pa, United States, irit/inp-enseeiht,university of toulouse,toulouse, France, center for computational biology and bioinformatics,university of michigan,ann arbor,mi,united states,department of biomedical engineering,university of michigan,ann arbor,mi,united states,department of chemical engineering,university of michigan,ann arbor,mi, United States, department of medicine,duke university,durham,nc, United States, department of medicine,duke university,durham,nc, United States, institute for genome sciences and policy,duke university,durham,nc,united states,department of medicine,duke university,durham,nc, United States, department of medicine,school of medicine,emory university,atlanta,ga, United States, department of medicine,duke university,durham,nc, United States, department of electrical and computer engineering,duke university,durham,nc, United States, center for pediatric genomic medicine,children's mercy hospital,kansas city,mo, United States, institute for genome sciences and policy,duke university,durham,nc,united states,department of medicine,duke university,durham,nc, United States, institute for genome sciences and policy,duke university,durham,nc,united states,department of medicine,duke university,durham,nc, United States, center for computational biology and bioinformatics,university of michigan,ann arbor,mi,united states,department of statistics,university of michigan,ann arbor,mi,united states,department of biomedical engineering,university of michigan,ann arbor,mi,united states,department of electrical engineering and computer science,university of michigan,ann arbor,mi, United States
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Authors
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