Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA387035 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5588480.fastq.gz | Fastqsanger.gz | |||
| SRR5588490.fastq.gz | Fastqsanger.gz | |||
| SRR5588500.fastq.gz | Fastqsanger.gz | |||
| SRR5588510.fastq.gz | Fastqsanger.gz | |||
| SRR5588520.fastq.gz | Fastqsanger.gz |
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Project description:Human rhinoviruses (HRV) are a leading cause of the common cold, but can often lead to respiratory complications in immunocompromised groups, evidently in a species-associated manner. There has been a growing interest in what underlies the variability in the severity of induced disease between HRV A, B and C strains. Koo et al. investigated this at the transcriptomic level in respiratory epithelial cells harvested from children, hospitalised with acute wheezing episodes. (https://doi.org/10/4049/j.immunol.1800178). Interestingly, this study revealed significant alterations in the expression of key host cell splicing factors between some HRV-infected children and uninfected controls, mainly the Serine/Arginine Protein Kinase 1 (SRPK1) and several Serine/Arginine rich Splicing Factors (SRSFs). As these splicing factors regulate host splicing and translation, we hypothesise that HRV infection regulates the kinase SRPK1 and its substrates SRSFs to either dysregulate the splicing of host mRNAs performing antiviral functions and/or to alter the translation of viral proteins. We initiated this investigation by exploring HRV-A infections in-vitro using the strain HRV16. Here, we show that the pharmacological inhibition as well as the overexpression of SRPK1 has a direct and opposing effect on HRV16 infection in primary bronchial epithelial cells. In the same system, HRV16 infection led to significant downregulation at the gene, protein and phosphorylation levels of SRPK1 as well as of SRSF1, SRSF3 and SRSF6. Transcriptomic and alternative splicing (AS) bioinformatic analysis was performed using a physiologically relevant primary bronchial epithelial 3D model. This revealed the significantly altered AS of 1228 host genes during infection, with subsequent pathway analysis enriching the vast majority of these genes in cilia development and function networks. The impact of this effect has been demonstrated here, with HRV16 infection leading to significantly decreased cilia length and total numbers in our primary bronchial epithelial 3D model. Overall, this investigation has unravelled novel networks implemented during HRV infection and provided insights into the association of recurrent HRV infections at an early age with respiratory complications during development.
2025-09-30 | GSE203428 | 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 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:Despite being exposed to respiratory syncytial virus (RSV) infection multiple times in our lives, infants, older-adults, and immunocompromised patients are vulnerable to RSV-associated severe diseases, such as bronchiolitis and pneumonia. Respiratory viral infections are known to promote pulmonary fibrosis formation, which are often associated with a cellular remodeling process epithelial-mesenchymal transition (EMT). However, there is no information on whether RSV causes EMT in bronchial epithelial cells. Our results suggest that RSV-infection does not induce EMT in three different in vitro lung models: epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. Interestingly, RSV infection increased cell surface area and perimeter in the infected airway epithelium, which is distinct from the TGF-β1 driven cell elongation. Genome-wide transcriptome analysis also revealed that RSV infection is not involved in cell motility and locomotion. Thus, our results suggest that RSV infection does not induce EMT in the airway epithelium
2023-06-13 | GSE189537 | GEO
Project description:Human rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in humans and highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examined the links between viral host defense, cellular metabolism, and epithelial barrier function. We observed that early HRV-C15 infection induced a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induced ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1alpha regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.
2021-04-30 | PXD024591 | Pride
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:We studied RSV infection in an appropriate in vitro model of respiratory epithelium, a pseudostratified and fully differentiated mucociliary epithelium of normal human bronchial epithelial (NHBE) cells. RSV infection increased actin cytoskeleton without compromising adherent-, tight-, and tricellular-junctions as well as ciliary functions and epithelial tissue barrier integrity. This increased cytoskeleton depends on actin polymerization and the induction of proinflammatory cytokines and chemokines. Thus, we observed a novel signature “increased cytoskeleton” termed “cytoskeletal inflammation” in RSV-infected respiratory epithelium that presumably lacks classical antigen presenting cells, such as resident dendritic cells and macrophages. Our results suggest that RSV-induced cytoskeletal inflammation is a noncanonical earliest host response to the pathogen and contributes to airway inflammation.
2023-03-10 | GSE146795 | GEO
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 Protein P treated compared to Protein GTreated in BEBM medium One condition design comparision of two strains including a dye swap
2014-06-21 | E-GEOD-58424 | biostudies-arrayexpress
Project description:Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-$\upkappa$B transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators. To better understand the pleiotropic regulatory function of BRD4, we examine the BRD4 interactome and identify how RSV infection dynamically alters it. To accomplish these goals, we leverage native immunoprecipitation and Parallel Accumulation – Serial Fragmentation (PASEF) mass spectrometry to examine BRD4 complexes isolated from human alveolar epithelial cells in the absence or presence of RSV infection. In addition, we explore the role of BRD4's acetyl-lysine binding bromodomains in mediating these interactions by using a highly selective competitive bromodomain inhibitor. We identify 101 proteins that are significantly enriched in the BRD4 complex and are responsive to both RSV-infection and BRD4 inhibition. These proteins are highly enriched in transcription factors and transcriptional coactivators. Among them, we identify members of the AP1 transcription factor complex, a complex important in innate signaling and cell stress responses. We independently confirm the BRD4/AP1 interaction in primary human small airway epithelial cells. We conclude that BRD4 recruits multiple transcription factors during RSV infection in a manner dependent on acetyl-lysine binding domain interactions. This data suggests that BRD4 recruits transcription factors to target its RNA processing complex to regulate gene expression in innate immunity and inflammation.
2021-03-17 | PXD023983 | Pride