Host gene expression signatures of influenza A H1N1 and H3N2 virus infection in adults
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Geoffrey Ginsburg
PROVIDER: E-GEOD-52428 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Diagnosis of acute respiratory viral infection is currently based on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis. We used microarrays to capture peripheral blood gene expression at baseline and time of peak symptoms in healthy volunteers infected intranasally with influenza A H3N2, respiratory syncytial virus or rhinovirus. We determined groups of coexpressed genes that accurately classified symptomatic versus asymptomatic individuals. We experimentally inoculated healthy volunteers with intranasal influenza, respiratory syncytial virus or rhinovirus. Symptoms were documented and peripheral blood samples drawn into PAXgene tubes for RNA isolation.
2009-08-06 | E-GEOD-17156 | biostudies-arrayexpress
Project description:Diagnosis of influenza A infection is currently based on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with influenza A virus infection represents a novel approach to infection diagnosis We used microarrays to assay peripheral blood gene expression at baseline and every 8 hours for 7 days following intranasal influenza A H1N1 or H3N2 inoculation in healthy volunteers. We determined groups of coexpressed genes that classified symptomatic influenza infection. We then tested this gene expression classifier in patients with naturally acquired respiratory illness.
2013-11-16 | GSE52428 | GEO
Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. Healthy adults were invited to enroll to be followed for acute respiratory illness (ARI) through two consecutive influenza seasons 2009-2010 and 2010-2011. After subjects provided consent, baseline blood specimens were obtained during enrollment. Subjects were given thermometers and instructions to call and report for evaluation within 48 hours of ARI onset. Those persons who had a new ARI were seen within 48 hours of onset (day 0) and 2, 4, and 6 days later for repeat evaluation, blood specimen collections, and medical care (including the antiviral zanamivir if indicated) and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection by RT-PCR on day 0 and day 2. Surveillance for influenza was terminated after 5.5 months; all subjects were asked to return for specimen collection and to provide a medical and ARI history in spring of next year. Serum specimens obtained at baseline, day 0 and day 21 visits for illnesses, and the terminal visit were tested simultaneously using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains. Peripheral blood RNA (PaxGene) obtained from blood specimens at each visit were analyzed using Illumina Human HT-12 v4. The study was repeated 2010-2011. A total of 880 arrays, corresponding to 133 individuals, passed quality control and are included in this data set.
2015-04-28 | E-GEOD-68310 | biostudies-arrayexpress
Project description:<p>The overall purpose of this study is to investigate the host genetic factors in response to influenza virus infection, with the focus on influenza vaccination in the first substudy "Adult Influenza Vaccine Genetics" and with the focus on influenza natural infection and other acute respiratory infections (ARIs) in the second substudy "Acute Viral Respiratory Infection Genetics". In the first substudy, healthy adults were enrolled in 2008 (male cohort) and 2010 (female cohort) and immunized with seasonal influenza vaccine. In the second substudy, healthy adults were invited to enroll to be followed for acute respiratory illness through two consecutive influenza seasons 2009-2010 and 2010-2011. Peripheral blood genomic DNA samples were collected from all the subjects, and time-series RNA and serum samples were obtained pre- and post- immunization/infection. Genotyping was carried out on peripheral blood genomic DNA samples using Illumina HumanOmniExpress-12 v1 arrays. Peripheral blood RNA samples obtained at each visit were analyzed using Illumina Human HT-12 (for all the samples) and HiSeq 2000 (for 130 samples in the "Acute Viral Respiratory Infection Genetics" study). Serum specimens were tested using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains.</p> <p>A detailed description of each substudy is provided under their own pages below and via the grouping tool in the right-hand box: <ul> <li><a href="./study.cgi?study_id=phs000635">phs000635</a> Adult Influenza Vaccine Genetics</li> <li><a href="./study.cgi?study_id=phs001031">phs001031</a> Acute Viral Respiratory Infection Genetics</li> </ul> </p>
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Project description:Despite increases in vaccination coverage, reductions in influenza-related mortality have not been observed. Better vaccines are therefore required and influenza challenge studies can be used to test the efficacy of new vaccines. However, this requires the accurate post-challenge classification of subjects by outcome, which is limited in current methods that use artificial thresholds to assign “symptomatic” and “asymptomatic” phenotypes. We present data from an influenza challenge study in which 22 healthy adults (11 vaccinated) were inoculated with H3N2 influenza (A/Wisconsin/67/2005). We generated genome-wide gene expression data from peripheral blood taken immediately before the challenge and at 12, 24, and 48 hours post-challenge. Variation in symptomatic scoring was found among those with laboratory confirmed influenza. By combining the dynamic transcriptomic data with the clinical parameters this variability can be reduced. We identified four subjects with severe laboratory confirmed flu that show differential gene expression in 1,103 probes 48 hours post-challenge compared to the remaining subjects. We have further reduced this profile to 6 genes that can be used to define these subjects. We have used this gene set to predict symptomatic infection from an independent study. This analysis gives further insight into host-pathogen interactions during influenza infection. However, the major potential value is in the clinical trial setting by providing a more quantitative method to better classify symptomatic individuals post influenza challenge. Twenty two healthy volunteers were enrolled for an influenza challenge study. Eleven were vaccinated thirty days before challenge with H3N2 influenza. Whole blood was collected in PAXgene tubes prior to influenza challenge and then at three further timepoints (12, 24 and 48 hours post-challenge).
2014-11-06 | E-GEOD-61754 | biostudies-arrayexpress
Project description:Diagnosis of acute respiratory viral infection is currentlybased on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis. We used microarrays to capture peripheral blood gene expression at baseline and time of peak symptoms in healthy volunteers infected intranasally with influenza A H3N2, respiratory syncytial virus or rhinovirus. We determined groups of coexpressed genes that accurately classified symptomatic versus asymptomatic individuals.
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Project description:WT or IFITM3-KO mice were infected with PR8 H1N1 influenza virus and reinfected with X31 H3N2 influenza virus
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Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.
2015-04-28 | GSE68310 | GEO
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness. 273 subjects were ascertained for this analysis. This included 88 patients with non-infectious illness, 115 with viral acute respiratory infection, and 70 with bacterial acute respiratory infection. Samples were obtained at the time of enrollment, which was at initial clinical presentation. Total RNA was extracted from human blood using the PAXgene Blood RNA Kit. Microarray data were generated using the GeneChip Human Genome U133A 2.0 Array. Microarrays were generated in two microarray batches with seven overlapping samples giving rise to 280 total microarray experiments.
2016-01-20 | E-GEOD-63990 | biostudies-arrayexpress
Project description:The transcriptional responses of human hosts towards influenza viral pathogens are important for understanding virus-mediated immunopathology. Despite great advances gained through studies using model organisms, the complete temporal host transcriptional responses in a natural human system are poorly understood. In a human challenge study using live influenza (H3N2/Wisconsin) viruses, we conducted a clinically uninformed (unsupervised) factor analysis on gene expression profiles and established an ab initio molecular signature that strongly correlates to symptomatic clinical disease. This is followed by the identification of 42 biomarkers whose expression patterns best differentiate early from late phases of infection. In parallel, a clinically informed (supervised) analysis revealed over-stimulation of multiple viral sensing pathways in symptomatic hosts and linked their temporal trajectory with development of diverse clinical signs and symptoms. The resultant inflammatory cytokine profiles were shown to contribute to the pathogenesis because their significant increase preceded disease manifestation by 36 hours. In subclinical asymptomatic hosts, we discovered strong transcriptional regulation of genes involved in inflammasome activation, genes encoding virus interacting proteins, and evidence of active anti-oxidant and cell-mediated innate immune response. Taken together, our findings offer insights into influenza virus-induced pathogenesis and provide a valuable tool for disease monitoring and management in natural environments. During the challenge study, subjects had peripheral blood taken 24 hours prior to inoculation with virus (baseline), immediately prior to inoculation (pre-challenge) and at set intervals (8 hour intervals) following challenge. RNA was extracted at Expression Analysis (Durham, NC) from whole blood using the PAXgene™ 96 Blood RNA Kit (PreAnalytiX, Valencia, CA) employing the manufacturer's recommended protocol. While whole blood RNA is initially extracted, a secondary procedure (B-globin reduction) was then employed to remove the contribution of red blood cell (RBC) RNA to the total RNA. A set of four peptide nucleic acid (PNA) oligomers whose sequences are complementary to the 3’ portions of the alpha and beta hemoglobin RNA transcripts were added to reduce globin RNA transcription due to RBC. The inhibition of globin cDNA synthesis dramatically reduces the relative amount of anti-sense, biotin-labeled cRNA corresponding to the hemoglobin transcripts. Hybridization and microarray data collection was performed using the Human Genome U133A 2.0 Array (Affymetrix, Santa Clara, CA) and expression profiles were pre-processed using robust multi-array (RMA) method
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