Host and Viral Determinants of Respiratory Syncytial Virus-induced Airway Mucus.
Ontology highlight
ABSTRACT:
SUBMITTER: Stier MT
PROVIDER: S-EPMC6322028 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Host and Viral Determinants of Respiratory Syncytial Virus-induced Airway Mucus.
Stier Matthew T MT Peebles R Stokes RS
Annals of the American Thoracic Society 20181101 Suppl 3
Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants worldwide each year. Both host and viral factors host factors predispose a subset of what appear to be healthy infants to severe RSV-induced disease. In this review, we outline many genetic and immunologic factors that contribute to airway obstruction that contributes to the severity of RSV infection. ...[more]
Similar Datasets
Project description:Severe RSV infection is the main cause of hospitalization to children under the age of five. The regulation of miRNAs on the severity of RSV infection is unclear. The aim of the study was to identify the critical differential expression miRNAs (DE miRNAs) that can regulate the pathological response in RSV-infected airway epithelial cells. In this study, miRNA and mRNA chips of RSV-infected airway epithelia from Gene Expression Omnibus (GEO) were screened and analysed, separately. DE miRNAs-targeted genes were performed for further pathway and process enrichment analysis. DE miRNA-targeted gene functional network was constructed on the basis of miRNA-mRNA interaction. The screened critical miRNA was also investigated by bioinformatics analysis. Then, RSV-infected human bronchial epithelial cells (HBECs) were constructed to verify the expression of the DE miRNAs. Finally, specific synthetic DE miRNAs mimics were used to confirm the effect of DE miRNAs on the RSV-infected HBECs. 45 DE miRNAs were identified from GEO62306 dataset. Our results showed that hsa-mir-34b-5p and hsa-mir-34c-5p decreased significantly in HBECs after RSV infection. Consistent with the biometric analysis, hsa-mir-34b/c-5p is involved in the regulation of mucin expression gene MUC5AC. In RSV-infected HBECs, the inducement of MUC5AC production by decreased hsa-mir-34b/c-5p was partly mediated through activation of c-Jun. These findings provide new insights into the mechanism of mucus obstruction after RSV infection and represent valuable targets for RSV infection and airway obstruction treatment.
| S-EPMC7687004 | biostudies-literature
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:Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV) had increased AR compared with OVA or RSV mice alone. Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice.To determine whether IL-17A increases AR and inflammation in the OVA/RSV model.Wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were harvested after infection. Cytokine expression was determined by ELISA in the lungs or BAL fluid. MLNs were restimulated with either OVA (323-229) peptide or RSV M2 (127-135) peptide and IL-17A protein expression was analysed. AR was determined by methacholine challenge.RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had decreased interferon-? protein expression compared with RSV mice. OVA/RSV mice had increased IL-23p19 mRNA expression in lung homogenates compared with mock, OVA or RSV mice. Unexpectedly, IL-17A KO OVA/RSV mice had increased AR compared with WT OVA/RSV mice. Furthermore, IL-17A KO OVA/RSV mice had increased eosinophils, lymphocytes and IL-13 protein expression in BAL fluid compared with WT OVA/RSV mice.IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. This finding is important because IL-17A has been identified as a potential therapeutic target in asthma, and inhibiting IL-17A in the setting of virally-induced asthma exacerbations may have adverse consequences.
| S-EPMC3916091 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide. While most develop a mild, self-limiting illness, some develop severe acute lower respiratory infection and persistent airway disease. Exposure to ambient particulate matter has been linked to asthma, bronchitis, and viral infection in multiple epidemiological studies. We hypothesized that coexposure to nanoparticles worsens RSV-induced airway epithelial barrier dysfunction. Bronchial epithelial cells were incubated with titanium dioxide nanoparticles (TiO2-NP) or a combination of TiO2-NP and RSV. Structure and function of epithelial cell barrier were analyzed. Viral titer and the role of reactive oxygen species (ROS) generation were evaluated. In vivo, mice were intranasally incubated with TiO2-NP, RSV, or a combination. Lungs and bronchoalveolar lavage (BAL) fluid were harvested for analysis of airway inflammation and apical junctional complex (AJC) disruption. RSV-induced AJC disruption was amplified by TiO2-NP. Nanoparticle exposure increased viral infection in epithelial cells. TiO2-NP induced generation of ROS, and pretreatment with antioxidant, N-acetylcysteine, reversed said barrier dysfunction. In vivo, RSV-induced injury and AJC disruption were augmented in the lungs of mice given TiO2-NP. Airway inflammation was exacerbated, as evidenced by increased white blood cell infiltration into the BAL, along with exaggeration of peribronchial inflammation and AJC disruption. These data demonstrate that TiO2-NP exposure exacerbates RSV-induced AJC dysfunction and increases inflammation by mechanisms involving generation of ROS. Further studies are required to determine whether NP exposure plays a role in the health disparities of asthma and other lung diseases, and why some children experience more severe airway disease with RSV infection.
| S-EPMC7518063 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention. DNA virus infections have been reported to induce modifications in cellular circRNA transcriptomes and express viral circRNAs. However, the identification and expression of cellular and viral circRNAs are unknown in the context of respiratory syncytial virus (RSV), a human RNA virus with no effective treatments or vaccines. Here, we report a comprehensive identification of the cellular and viral circRNAs induced by RSV infection in A549 cells with high-throughput sequencing. In total, 53,719 cellular circRNAs and 2,280 differentially expressed cellular circRNAs were identified. Trend analysis further identified three significant expression pattern clusters, which were related to the antiviral immune response according to gene enrichment analysis. Subsequent results showed that not only RSV infection but also poly(I·C) treatment and another RNA virus infection induced the upregulation of the top 10 circRNAs from the focused cluster. The top 10 circRNAs generally inhibit RSV replication in turn. Moreover, 1,254 viral circRNAs were identified by the same circRNA sequencing. The induced expression of viral circRNAs by RSV infection was found not only in A549 cells but also in HEp-2 cells. Additionally, we profiled the general characteristics of both cellular and viral circRNAs such as back-splicing signals, etc. Collectively, RSV infection induced the differential expression of cellular circRNAs, some of which affected RSV infection, and RSV also expressed viral circRNAs. Our study reveals novel layers of host-RSV interactions and identifies cellular or viral circRNAs that may be novel therapeutic targets or biomarkers. IMPORTANCE Noncoding RNAs (ncRNAs) demonstrate substantial roles in cell-virus interactions. Circular RNAs (circRNAs) are a newly identified class of ncRNAs that have gained increased attention recently. DNA virus infections have been reported to induce modifications in cellular circRNA transcriptomes and express viral circRNAs. However, the identification and expression of cellular and viral circRNAs are unknown in the context of respiratory syncytial virus (RSV), a human RNA virus with no effective treatments or vaccines. Here, we report a comprehensive identification of the cellular and viral circRNAs induced by RSV infection by high-throughput sequencing. We revealed that RSV infection induces the differential expression of cellular circRNAs, some of which affected RSV infection, and that RSV also expresses viral circRNAs. Our study reveals novel layers of host-RSV interactions and identifies cellular or viral circRNAs that may be novel therapeutic targets or biomarkers.
| S-EPMC8649777 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) is the leading cause of respiratory failure and viral death in infants. Abundant airway mucus contributes to airway obstruction in RSV disease. Interleukin-13 (IL-13) is a mediator of pulmonary mucus secretion. It has been shown that infection of BALB/c mice with the RSV line 19 strain but not with the RSV A2 laboratory strain results in lung IL-13 and mucus expression. Here, we sequenced the RSV line 19 genome and compared it to the commonly used A2 and Long strains. There were six amino acid differences between the line 19 strain and both the A2 and Long RSV strains, five of which are in the fusion (F) protein. The Long strain, like the A2 strain, did not induce lung IL-13 and mucus expression in BALB/c mice. We hypothesized that the F protein of RSV line 19 is more mucogenic than the F proteins of A2 and Long. We generated recombinant, F-chimeric RSVs by replacing the F gene of A2 with the F gene of either line 19 or Long. Infection of BALB/c mice with RSV rA2 line 19F resulted in lower alpha interferon lung levels 24 h postinfection, higher lung viral load, higher lung IL-13 levels, greater airway mucin expression levels, and greater airway hyperresponsiveness than infection with rA2-A2F or rA2-LongF. We identified the F protein of RSV line 19 as a factor that plays a role in pulmonary mucin expression in the setting of RSV infection.
| S-EPMC2668460 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-29 | GSE232687 | GEO
Project description:Respiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. It has been shown that infection of BALB/cJ mice with RSV clinical isolate A2001/2-20 (2-20) results in a higher early viral load, greater airway necrosis, and higher levels of interleukin-13 (IL-13) and airway mucin expression than infection with RSV laboratory strain A2. We hypothesized that the fusion (F) protein of RSV 2-20 is a mucus-inducing viral factor. In vitro, the fusion activity of 2-20 F but not that of A2 F was enhanced by expression of RSV G. We generated a recombinant F-chimeric RSV by replacing the F gene of A2 with the F gene of 2-20, generating A2-2-20F. Similar to the results obtained with the parent 2-20 strain, infection of BALB/cJ mice with A2-2-20F resulted in a higher early viral load and higher levels of subsequent pulmonary mucin expression than infection with the A2 strain. A2-2-20F infection induced greater necrotic airway damage and neutrophil infiltration than A2 infection. We hypothesized that the neutrophil response to A2-2-20F infection is involved in mucin expression. Antibody-mediated depletion of neutrophils in RSV-infected mice resulted in lower tumor necrosis factor alpha levels, fewer IL-13-expressing CD4 T cells, and less airway mucin production in the lung. Our data are consistent with a model in which the F and attachment (G) glycoprotein functional interaction leads to enhanced fusion and F is a key factor in airway epithelium infection, pathogenesis, and subsequent airway mucin expression.
| S-EPMC3753991 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) is the most prevalent viral etiological agent of acute respiratory tract infection. Although RSV affects people of all ages, the disease is more severe in infants and causes significant morbidity and hospitalization in young children and in the elderly. Host factors, including an immature immune system in infants, low lymphocyte levels in patients under 5 years old, and low levels of RSV-specific neutralizing antibodies in the blood of adults over 65 years of age, can explain the high susceptibility to RSV infection in these populations. Other host factors that correlate with severe RSV disease include high concentrations of proinflammatory cytokines such as interleukins (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and thymic stromal lymphopoitein (TSLP), which are produced in the respiratory tract of RSV-infected individuals, accompanied by a strong neutrophil response. In addition, data from studies of RSV infections in humans and in animal models revealed that this virus suppresses adaptive immune responses that could eliminate it from the respiratory tract. Here, we examine host factors that contribute to RSV pathogenesis based on an exhaustive review of in vitro infection in humans and in animal models to provide insights into the design of vaccines and therapeutic tools that could prevent diseases caused by RSV.
| S-EPMC6753334 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) most often causes severe respiratory disease in the very young and the elderly. Acute disease can also cause exacerbations of asthma in any age group. Recent findings provide insight into how the innate and adaptive immune systems respond to RSV infection and provide preliminary evidence that these effects vary significantly by RSV strain and host. Components of cell signaling pathways that induce inflammatory cytokine expression during the innate immune response and alter epithelial cell polarity through activating transcription factors, namely NF-?B, are now more clearly understood. New studies also reveal how RSV infection skews T helper (Th) cell differentiation away from the cell-mediated Th1 subset and towards the Th2 subset. There are also new data supporting preferential Th17 differentiation during RSV infection. In addition, effective immune system regulation of IL-10 expression and T regulatory cell (Treg) airway accumulation are essential for effective RSV clearance.
| S-EPMC3432290 | biostudies-literature