title: Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.
abstract: To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Laboratory of Systems Biology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Franco
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, Texas, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Quarles
authors.affiliation: Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, Texas, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Arden
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Bucasas
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Wells
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Diane
authors.initials: D
authors.lastname: Niño
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Gladys E
authors.initials: GE
authors.lastname: Zapata
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Belmont
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Couch
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003139:Common Cold / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology; D014158:Transcription, Genetic; D059467:Transcriptome; D055815:Young Adult