Human respiratory syncytial virus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1224818 | ENA |
REPOSITORIES: ENA
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Project description:Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in elderly populations. RSV clearance is delayed in individuals over 65 years of age, a finding that is recapitulated in the geriatric cotton rat model. Altered inflammatory responses in elderly populations have been implicated with impaired clearance of several pathogens but remain poorly described for RSV. We performed RNA sequencing (RNA-seq) and pathway analysis on lung tissue of RSV-infected adult and geriatric cotton rats to characterize differential host immune responses between these age groups. No differences in inflammatory gene expression were observed between uninfected adult and geriatric cotton rats. At day 1 post-infection, adult cotton rats expressed higher levels of several cytokines and transcription factors associated with acute inflammation and initiation of a Th1 response, including IFN-β, IL12, and Tbet, compared to geriatric cotton rats. By day 4 post-infection, adult cotton rats additionally expressed higher levels of effector molecules associated with Th1 responses, including IFN-γ. Pathway analysis showed significantly increased activation of several pro-inflammatory pathways in adults, including the Th1 pathway, macrophage classical (M1) activation, and pathogen-induced cytokine signaling. To evaluate lymphocyte Th1/Th2 polarization resulting from RSV infection in both age groups, we stimulated splenocytes with RSV peptides at day 28 post-infection and measured IFN-γ and IL-4 production by ELISA. Splenocytes of all adult cotton rats produced detectable IFN-γ and no IL-4, indicating Th1 polarization. Splenocytes of all geriatric cotton rats produced detectable IL-4, indicating Th2 polarization. Collectively, these results indicate that geriatric cotton rats exhibit impaired generation of a Th1 response and a decreased inflammatory response overall to RSV.
2026-06-01 | GSE297903 | GEO
Project description:Colonizing microbiota can differentially impact the outcomes of viral infections. While synergistic interactions between invading viruses and specific bacterial colonizers can enhance viral infectivity, resulting in severe disease, other bacteria can play a more antagonistic role by destabilizing viral particles, thus protecting against infection. Here, we explored whether Porphyromonas gingivalis (Pg), a periodontal bacterial pathogen that can translocate to the airways, increases susceptibility to infection with the respiratory syncytial virus (RSV) and Sendai virus (SeV). Using a model of primary human bronchial epithelial (HBE) air-liquid interface cultures, we found that Pg co-infection significantly reduced RSV infection by rapidly inactivating RSV particles. This protection was conferred by the proteolysis of RSV fusion and attachment proteins by Pg proteases (gingipains), thus limiting viral entry. Despite this initial bottleneck, RSV replication within Pg co-infected cells was higher, indicating Pg created an intracellular environment favorable for viral replication. RNA-seq studies revealed that Pg infection led to the broad suppression of interferons (IFNs), particularly IFN-λ, and downstream interferon-stimulated genes (ISGs). Thus, our data show that P. gingivalis initially restricts RSV infection by inactivating the virus but later facilitates viral replication by suppressing IFNs. Our findings are clinically relevant as RSV infections are significant health concerns in both pediatric populations and older adults, who have a higher prevalence of periodontitis.
2026-04-17 | GSE281938 | GEO
Project description:Human Respiratory Syncytial Virus (hRSV) is a prevalent pathogen posing significant risks to infants and older adults. While the roles of RSV non-structural proteins NS1 protein in modulating host immune responses remains poorly defined, its potential impact on viral pathogenicity is critical. We employed CUT&RUN of NS1, Mediator, and ATF3 in WT NS1 and mutant NS1 expressing A549 cells and bulk RNA sequencing of WT and mutant NS1-expressing A549 (GSE155151) and RSV infection in human lung air-liquid interface (ALI) cultures to elucidate the perterbations of transcriptional regulatory control induced by NS1. Coupled with our earlier work, these epigenomic and transcriptomic profiling datasets provides deeper insights into the molecular mechanisms through which RSV NS1 protein disrupts host immune functions.
2025-03-09 | GSE270463 | GEO
Project description:Respiratory Syncytial Virus (RSV) infection often elicits ineffective long-term immune responses due to inefficient immune priming, complicating disease management and vaccine development. Dendritic cells (DCs) play a pivotal role as initiators of immune responses and viral clearance. However, the direct impact of RSV on antigen presentation mechanisms remains poorly understood. In this study, we characterized the impact of RSV on blood DCs, revealing high HLA-DM expression- a unique phenotype closely associated with wider DC peptide repertoire but compromised T cell engagement during antigen presentation. We found inhibition of TBK1, a key kinase in Type I Interferon responses, restored antigen presenting capacities in RSV-infected DCs. This underscores the critical role of TBK1-mediated mechanisms in initiating adaptive immunity and downstream T cell responses during RSV infection. Our findings fill a significant knowledge gap in RSV pathogenesis, suggesting TBK1 as a potential molecular target for enhancing DC responses and immune protection against RSV.
2026-06-18 | GSE334417 | GEO
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:Purpose: To understand how dexamethasone has beneficial effects on reducing mucus production but inhibits viral defense mechanisms Methods: RSV-infected mouse lungs and various cell lines, plus and minus dexamethason, were examined by RNAseq, and pathway analysis of differentially-expressed genes were compared Results: Using RNA-seq we identified a subset of cytokines that were induced by RSV and repressed by dexamethasone. Interestingly, while RSV induced interferons (IFNs) and IFN stimulated genes (ISGs), dexamethasone treatment did not affect the expression of these genes or antiviral IFN signaling pathways as has been observed with glucocorticoid treatment of other respiratory viruses [13]. Using an unbiased approach, we found that certain RSV-driven gene expression networks and genes were specifically modulated by dexamethasone treatment. Importantly, dexamethasone also reduced RSV clearance in vivo, which correlated with a reduction in specific immune response markers. Conclusion: Our results support the possibility that the beneficial anti-inflammatory effects of dexamethasone treatment are counterbalanced by the increased viral load in patients, accounting for the lack of clinical benefit derived from treatment during RSV infection.
2019-11-19 | GSE140226 | GEO
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
2025-04-21 | GSE260752 | GEO
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
2025-04-21 | GSE263272 | GEO
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
2025-04-21 | GSE263271 | 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