Deciphering the gene expression response of human immune cells to stimulation with RSV in the context of antibodies
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59391 | GEO | 2015/10/06
SECONDARY ACCESSION(S): PRJNA255237
REPOSITORIES: GEO
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Project description:While the majority of infants infected with respiratory syncytial virus (RSV) exhibit mild or no symptoms, approximately 3 million children under the age of five are hospitalized every year due to complications from RSV. This research sought to explore the biological processes and related biomarkers responsible for the varied manifestations of RSV disease in young infants. The goal is to pave the way for a more precise categorization of RSV-infected infants based on their medical requirements. Whole blood samples are collected from infant case-control cohort study, the RESCEU case-control cohort is a multinational, multicenter, observational study (clinical trial registration number: NCT03756766). Infants < 12 months old with RSV disease were recruited from the University Medical Center Utrecht (UMCU) in The Netherlands, Hospital Clínico Universitario de Santiago (SERGAS) in Spain, Imperial College (IMPERIAL) National Health Service Trust (NHS) and Oxford University Hospital NHS Trust (OXFORD) in the United Kingdom during the RSV seasons 2017-2018, 2018-2019, and 2019-2020. Healthy controls without underlying comorbidities were recruited outside of the RSV season. Eligibility criteria included hospitalization for less than 48 hours at enrolment or within 96 hours of disease onset, no previous receipt of medications to treat RSV infection, no prior exposure to an investigational RSV vaccine or medication, no previous receipt of immunoglobulins or monoclonal antibodies, and had not used montelukast or oral steroids within seven days before enrolment. Infants with co-morbidities were not evaluated in the manuscript. RSV was detected using RSV point-of-care test (POCT) by either a rapid antigen detection test (Alere I) (Alere Inc, Waltham, Massachusetts) or rapid RSV polymerase chain reaction (PCR) test at the hospital setting, or a RSV PCR test at the laboratory. Convalescence samples were collected 7 ±1 weeks after a positive RSV diagnostic test result. We used microarray to assist us to identify biomarkers for severe RSV disease.
2024-01-03 | GSE246622 | GEO
Project description:The aim of this investigation was two-fold: i) to describe miRNAs involved in the immune response to Respiratory syncytial virus (RSV) in a clinical setting in order to inform further research of immune system regulation by miRNAs in RSV or other infections; ii) to discover differences in miRNA expression between disease severity groups. We have therefore profiled miRNA in cytology brushings of the nasal mucosa in infants with RSV disease, comparing them to healthy infants. miRNA microarray identified 26 differentially regulated miRNA which were subsequently analyzed by RT-qPCR.
2014-10-15 | GSE62306 | GEO
Project description:This study measured the cytokine, cellular and transcriptomic response to RSV and compared these between preterm and term infants CBMC responses
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Project description:RSV, a leading cause of severe respiratory illnesses in vulnerable populations, lacks effective, affordable treatments for pediatric use. The potential of traditional Chinese medicine for relieving viral symptoms prompted this investigation into Xuanfei Formula (XFF) as an anti-RSV agent. This study employed H&E staining, cytokine profiling, and RSV titer quantification in BALB/c mice to evaluate the impact of XFF on RSV infection. Strikingly, immediate post-treatment observation showed a precipitous drop in both serum pro-inflammatory cytokine levels and pulmonary RSV-N gene copies in comparison to infected controls, suggesting XFF’s direct anti-RSV action. Transcriptome analyses were used to pinpointed the underlying mechanism behind formula’s immune-independent anti-RSV, a leading cause of severe respiratory illnesses in vulnerable populations, lacks effective, affordable treatments for pediatric use. The potential of traditional Chinese medicine for relieving viral symptoms prompted this investigation into Xuanfei Formula (XFF) as an anti-RSV agent. This study employed H&E staining, cytokine profiling, and RSV titer quantification in BALB/c mice to evaluate the impact of XFF on RSV infection. Strikingly, immediate post-treatment observation showed a precipitous drop in both serum pro-inflammatory cytokine levels and pulmonary RSV-N gene copies in comparison to infected controls, suggesting XFF’s direct anti-RSV action. Transcriptome analyses were used to pinpointed the underlying mechanism behind formula’s immune-independent anti-RSV effects during infection.
2024-04-25 | GSE263754 | GEO
Project description:<p>A prospective multi-year clinical translational study including three cohorts of term infants experiencing their first Respiratory Syncytial Virus (RSV) season. All infants are less than or equal to nine months of age at study entry. The three subject cohorts represent the full spectrum of RSV disease severity and include a birth cohort, a cohort of infants hospitalized for RSV disease and infants evaluated at ambulatory settings for RSV infection. All infants are followed longitudinally and evaluated at recognition of acute RSV infection and twice during convalescence. Innate and adaptive immune status are comprehensively measured in association with clinical, environmental, viral, and bacteriologic factors. Genome-wide expression is assessed in the nasal airways, and in sorted peripheral blood lymphocytes. The study goal is to Identify host responses to RSV infection and factors associated with severe disease. </p>
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Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection. Comparison of the Streptococcus pneumoniae D39 RSV treated compared to BSA Treated in BEBM medium One condition design comparision of two strains including a dye swap
2014-06-21 | E-GEOD-58425 | biostudies-arrayexpress
Project description:The objective of this study was to identify gene expression markers of disease severity in a cohort of RSV infected children Respiratory syncytial virus (RSV) is the number one pathogen causing lower respiratory tract infection that leads to hospitalization in young children. Despite growing insights in the disease pathogenesis, the clinical presentation in these children is highly variable and heterogeneous, and reliable markers predictive of disease progression are lacking. We characterized the host response to acute RSV infection to identify biomarkers associated with RSV disease and disease severity. Whole genome transcriptome was analysed early on the disease course in blood samples from otherwise healthy children <2 years of age, who were either hospitalized (n = 110) or evaluated as outpatients (n = 37) due to RSV infection. Age-matched non-RSV-infected healthy children (n = 51) were analysed in parallel. A clustering approach on the transcriptome data revealed biologically meaningful biomarkers associated with progression to severe RSV disease. Overall, the whole blood transcriptome pointed to alterations in frequency of specific immune cell types (neutrophils, T- and B-lymphocytes, NK cells, monocytes) in RSV-infected children. In addition, a cluster enriched for neutrophil degranulation genes, was highly correlated with clinical disease severity. The driver genes of this cluster (OLFM4, ELANE, MMP8, BPI, CEACAM8, LCN2, LTF and MPO) were selected and validated in independent existing transcriptomics datasets. We identified a set of genes involved in neutrophil degranulation as markers for RSV disease severity. Additional prospective studies using these markers are required to further confirm their value as predictive tool in routine clinical care.
2022-01-21 | GSE188427 | GEO
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:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.
2014-06-21 | GSE58425 | GEO
Project description:Human bronchial epithelial cells (BEAS-2B cells) were treated with RSV at 1.0 MOI for 4 and 24 hours or control (vehicle-treated for 4 hours). Global gene expression was measured by Affy Hu133 plus 2.0 microarray chips. Keywords: Inflammation, microtubules, RSV, time course
2006-05-01 | GSE3397 | GEO