Genome-wide analysis of whole blood transcriptional response to Respiratory Syncytial Virus, Influenza and Rhinovirus lower respiratory tract infection (LRTI) in children
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38900 | GEO | 2013/11/12
SECONDARY ACCESSION(S): PRJNA169158
REPOSITORIES: GEO
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Project description:Analysis of transcriptional profiles in whole blood from children < 2 years of age (and healthy matched controls) with RSV, rhinovirus and influenza infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity and that RSV infection induces a distinct host response compared with influenza and rhinovirus infection Total RNA extracted from whole blood (lysed in Tempus tubes) drawn from individual pediatric patients with acute RSV, influenza and Rhinovirus lower respiratory tract infection. A total of 241 samples are analyzed: 135 with acute RSV LRTI, 30 with Rhinovirus LRTI, 16 with influenza LRTI, 39 age-sex matched healthy controls and 21 samples obtained one month after the acute hospitalization in children with RSV. Samples GSM1226237-GSM1226272, which were hybridized to Platform GPL10558, were normalized separately from the other Samples in this Series, which were hybridized to Platform GPL6884. 'GSE38900_non-normalized_GSM1226237-GSM1226272.txt.gz' includes the non-normalized data for Samples GSM1226237-GSM1226272; 'GSE38900_non-normalized.txt.gz' includes the non-normalized data for the other Samples.
2013-11-12 | E-GEOD-38900 | biostudies-arrayexpress
Project description:Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Despite modest advances in the diagnosis and treatment of infections by these viruses, novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. From these data, we constructed a transcriptional regulatory network model that revealed shared and unique host responses to these viral infections such that after a lag of 4-8 hours, most cell host responses were similar for both viruses, while divergent host cell responses appeared after 24-48 hours. The similarities and differences in gene expression after epithelial infection of rhinovirus, influenza virus, or both viruses together revealed qualitative and quantitative differences in innate immune activation and regulation. These differences help explain the generally mild outcome of rhinovirus infections compared to influenza infections which can be much more severe. Human bronchial epithelial cells (BEAS-2B) were infected with rhinovirus, influenza virus or both viruses and RNAs were then profiled at 10 time points (2, 4, 6, 8, 12, 24, 26, 48, 60 and 72hrs)
2015-12-21 | E-GEOD-71766 | biostudies-arrayexpress
Project description:Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Despite modest advances in the diagnosis and treatment of infections by these viruses, novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. From these data, we constructed a transcriptional regulatory network model that revealed shared and unique host responses to these viral infections such that after a lag of 4-8 hours, most cell host responses were similar for both viruses, while divergent host cell responses appeared after 24-48 hours. The similarities and differences in gene expression after epithelial infection of rhinovirus, influenza virus, or both viruses together revealed qualitative and quantitative differences in innate immune activation and regulation. These differences help explain the generally mild outcome of rhinovirus infections compared to influenza infections which can be much more severe.
2015-12-21 | GSE71766 | GEO
Project description:we examine the effect of RSV infection in human small airway epithelial cells (hSAECs)
2021-02-26 | GSE167486 | GEO
Project description:Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.
2022-11-15 | MTBLS2352 | MetaboLights
Project description:Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
2016-05-09 | GSE77087 | GEO
Project description:Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections, however DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV-infection. Transcriptional profiling and biological network analysis identified transforming growth factor (TGF)-b and associated signaling molecules as differentially regulated in the two age groups. TGF-b1 was decreased in RSV-infected adult blood DCs, but increased in RSV-infected cord blood DCs. Co-culture of adult RSV-infected DCs with autologous T-cells induced secretion of interferon gamma (IFNg), IL-12p70, IL-2, and tumor necrosis factor alpha (TNFa). Conversely, co-culture of cord RSV-infected DCs and autologous T-cells induced secretion of IL-4, IL-6, IL-1b, and IL-17. Addition of purified TGF-b1 to adult DC-T cell co-cultures reduced secretion of IFNg, IL-12p70, IL-2, and TNFa, which addition of a TGF-b chemical inhibitor to cord DC-T cell co-cultures increased secretion of IL-12p70. These data suggest that TGF-b acts as a major regulator of RSV DC-T cell responses, which could contribute to immunopathology during infancy. Three sets of adult peripheral DCs were analyzed and three sets of cord blood DCs. The DCs from each donor were divided in half and either mock infected or infected with RSV and each (12 samples total) were used for affymetrix array analsis. The donor-matched mock infected DC hybridyzation was used as the reference sample for the RSV infected.
2010-11-01 | E-GEOD-24132 | biostudies-arrayexpress
Project description:<p>We studied a child with life-threatening and recurrent respiratory tract infections, caused by multiple viruses including rhinovirus, influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5 by Whole Exome Sequencing. MDA5-deficiency is a novel inborn error of innate immunity that results in impaired dsRNA-sensing, reduced IFN induction, and susceptibility to the common cold virus.</p>
| phs001235 | dbGaP
Project description:In this study we investigated whether there exists a genomic signature that can accurately predict the course of a respiratory syncytial virus (RSV) infection in hospitalized young infants. We used early blood microarray transcriptome profiles from 39 infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease.
2016-11-11 | E-MTAB-5195 | biostudies-arrayexpress
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