Distinct peripheral blood mononuclear cells transcriptional modules in the response to human respiratory syncytial virus or human rhinovirus in hospitalized infants with bronchiolitis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124124 | GEO | 2019/03/19
REPOSITORIES: GEO
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Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
2018-03-21 | GSE103842 | GEO
Project description:We report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors. RNA-seq analysis identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3). We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets. Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation. Differentiated air-liquid interface cultured human airway epithelial cell mRNA profiles from 6 asthmatic and 6 non-asthmatic donors after 24 hour treatment with either HRV or vehicle control were generated by deep sequencing, using Illumina HiSeq 2000.
2015-03-01 | E-GEOD-61141 | biostudies-arrayexpress
Project description:Human Rhinovirus (HRV) infection can trigger exacerbations of asthma. Understanding of the mechanisms provoking airway inflammation and remodeling in asthma, as well as the pathogenic mechanisms of HRV infection and its association with asthma exacerbations, may offer significant opportunities for improved disease management. Genome-wide expression analysis of HRV type 1A-infected primary bronchial epithelial (PBE) cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of gene expression after HRV infection in vitro. Keywords: response to rhinovirus infection
2008-11-01 | GSE13396 | GEO
Project description:Major- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus. RNA sequencing of monocyte-derived macrophages after mock infection or infection by HRV16 or HRV1A
2014-03-14 | E-GEOD-55271 | biostudies-arrayexpress
Project description:Major- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus.
2014-03-14 | GSE55271 | GEO
Project description:Distinct peripheral blood mononuclear cells transcriptional modules in the response to human respiratory syncytial virus or human rhinovirus in hospitalized infants with bronchiolitis
| PRJNA510927 | ENA
Project description:Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence.
2018-12-24 | GSE113210 | GEO
Project description:Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence.
2018-12-24 | GSE113209 | GEO
Project description:Acute viral bronchiolitis (PBMC)
| PRJNA450430 | ENA