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PROVIDER: PRJNA613296 | ENA |
REPOSITORIES: ENA
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Project description:Defective viral genomes determine respiratory syncytial virus disease severity in adult and children cohorts
| PRJNA612442 | ENA
Project description:This series includes 278 microarrays used to detect respiratory viruses in a set of nasopharyngeal lavage specimens from children with respiratory tract infections Objective: To assess the utility of a pan-viral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections. Study Design: The Virochip was compared to conventional clinical direct fluorescent antibody (DFA) and PCR-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity 85-90%, specificity 99%, PPV 94-96%, NPV 97-98%) in the detection of respiratory syncytial virus, influenza A, and rhino-/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions: Given its favorable sensitivity and specificity profile and greatly expanded spectrum of detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric respiratory tract infections. Keywords: viral detection The series includes 278 clinical specimens
2010-05-26 | E-GEOD-10294 | biostudies-arrayexpress
Project description:Respiratory syncytial virus (RSV) causes severe disease mostly in infants; however, mechanisms of age association remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigate whether age regulates RSV-epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibits cytopathy and mucus hyperplasia, and neonatal epithelium has more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells display age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitates viral spread. In contrast, SARS-CoV-2 infection of ciliated cells has no effect on STAT3 activation and is not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.
2024-09-01 | GSE242397 | GEO
Project description:We report the analysis of nasal curettage cells by RNAseq collected at pre-symptomatic timepoints in healthy adults experimentally challenged with respiratory syncytial virus (RSV). Following inoculation, 57% of participants developed PCR-confirmed infection. Prior to viral challenge, 80 differentially expressed genes were identified that associated with susceptibility to symptomatic infection. At day 3, 87 differentially expressed genes were associated with protection. Thus, we showed that the nasal mucosa at the time of virus exposure and during the incubation phase correlate with susceptibiltiy and protection from respiratory viral infection.
2020-09-01 | GSE155237 | GEO
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:Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. In conclusion, by combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection. Samples were taken of 26 patients with acute RSV infections, divided into mild (n=9), moderate (n=9) and severe (n=8) disease. From moderate and severe diseased patients recovery samples were obtained as well.
2015-06-06 | E-GEOD-69606 | biostudies-arrayexpress
Project description:Purpose: The aim of this study is to determine the expression profile in whole blood samples of children infected with respiratory syncytial virus and other respiratory viruses. Method: Host mRNA profiles in whole blood samples of children were generated by next-generation sequencing using Illumina Hiseq. Sequence reads were trimmed for adapter using skewer, mapped to reference human genome using STAR, and quantified using RSEM. Differential expression analysis was performed using DESeq2. Results: Transcriptional module analysis revealed dysregulation of genes related to inflammatory response, neutrophils, monocytes, B-cell and T-cell response. Conclusion: This study showed an imbalance in innate and adaptive immune responses in children with respiratory virus infections. This study also showed that NGS provides a comprehensive assessment of transcripts in whole blood samples.
2021-01-29 | GSE155925 | GEO
Project description:Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Despite posing substantial health risks, airway immune responses in early life remain largely unexplored. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular networks for influenza A and respiratory syncytial virus, emphasizing highly relevant virus-specific pathways. This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers novel insights that should enable a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.
2024-11-06 | PXD042209 | Pride
Project description:This series includes 278 microarrays used to detect respiratory viruses in a set of nasopharyngeal lavage specimens from children with respiratory tract infections Objective: To assess the utility of a pan-viral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections. Study Design: The Virochip was compared to conventional clinical direct fluorescent antibody (DFA) and PCR-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity 85-90%, specificity 99%, PPV 94-96%, NPV 97-98%) in the detection of respiratory syncytial virus, influenza A, and rhino-/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions: Given its favorable sensitivity and specificity profile and greatly expanded spectrum of detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric respiratory tract infections. Keywords: viral detection
2008-07-09 | GSE10294 | GEO