RV infections in asthmatics increase ACE2 expression and stimulate cytokine pathways implicated in COVID19
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ABSTRACT:
PROVIDER: PRJNA627860 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR11604700.fastq.gz | Fastqsanger.gz | |||
| SRR11604701.fastq.gz | Fastqsanger.gz | |||
| SRR11604702.fastq.gz | Fastqsanger.gz | |||
| SRR11604703.fastq.gz | Fastqsanger.gz | |||
| SRR11604704.fastq.gz | Fastqsanger.gz |
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Project description:We present evidence that (1) viral respiratory infections are potential mechanisms of ACE2 overexpression in patients with asthma and (2) ACE activation regulates multiple cytokine anti-viral responses that could explain a mechanism for cytokine surge and associated tissue damage. These results suggest that the recent finding of severe COVID-19 in asthma patients with recent exacerbations may be attributable to synergistic biomolecular interactions with viral co-infections.
2020-04-25 | GSE149273 | GEO
Project description:Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results: AsResults: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic. a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.
2021-07-15 | GSE179156 | GEO
Project description:In this study a gene expression (i.e., RNAseq) analysis was performed in HEK293T-ACE2 cellular model upon infection with viral particle belonging to VOC Delta (MOI: 0.026) for 24 hours in order to have a global picture of the transcriptome landscape in response to early phase of infection of SARS-CoV-2 ( VOC Delta infection and to evaluate the role of Ca2+ in HEK293-ACE2 cellular model and transfer to homeostasis in SARS-COV-2 patients (by Pasqualino de Antonellis1-2* and Veronica Ferrucci 1-2* (first authors) et al. and Massimo Zollo1-2# (corresponding author). Manuscript in preparation 2022 July 15th 2022. Short title "ATP2B1 (PMCA1), regulated by FOXO3, influences susceptibility to severe COVID19".
2022-12-01 | E-MTAB-11973 | biostudies-arrayexpress
Project description:Up-regulation of ACE2, the SARS-CoV-2 Receptor, in Asthmatics on Maintenance Inhaled Corticosteroids
| PRJNA742421 | ENA
Project description:The homologous Ace2 and Swi5 transcription factors of Saccharomyces cerevisiae have identical DNA-binding domains, and both are cell cycle regulated. There are common target genes, as well as genes activated only by Ace2 and other genes activated only by Swi5. Keywords: genetic modification RNA was isolated from four strains: wild type, ace2 gene deletion, swi5 gene deletion, and the ace2 swi5 double gene deletion. RNAs from the three mutant strains were compared to wild type RNA in a microarray hybridization experiment.
2008-05-13 | E-GEOD-11380 | biostudies-arrayexpress
Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.
2020-10-01 | GSE154998 | GEO
Project description:Background: Evidence suggests that immune responses to rhinovirus A and C are altered in asthmatic children and rhinovirus species induce different types of antibody responses. Objective: To ascertain and compare the T-cell memory response induced by RV-A and RV-C in asthmatic and non-asthmatic children. Methods: Peripheral blood mononuclear cells from children who previously suffered asthma exacerbation (asthmatics) and non-asthmatic controls were stimulated in vitro with peptide formulations to induce representative species-specific responses to RV-A and RV-C. Expression of genes was measured by RNA-seq and differentially expressed genes were further analysed to identify enriched pathways and upstream regulators. Results: Responses to RV-A showed markedly higher upregulation of IFNG and the IFNG responsive genes CXCL9, 10 and 11 and STAT1 compared to RV-C. There was no reciprocal upregulation of Th2 cytokine genes or the Th2 chemokine genes CCL11, CCL17 and CCL22. RV-C but not RV-A induced high upregulation of CCL24 (eotaxin-2) in both non-asthmatic and asthmatic responses. Upstream regulator analysis showed both RV-A and, although to a diminished extent, RV-C induced predominant Th1 and inflammatory cytokine expression. The responses of asthmatics compared to non-asthmatics was diminished to both RV-A and RV-C while retaining the pattern for gene expression and upstream regulators characteristic of each species and there was no upregulation of Th2-type responses. All groups showed activation of the IL-17A pathway. Conclusions: RV-C induced memory cells with a lower IFNG type response than RV-A without Th2 upregulation. Asthmatics had lower recall responses than non-asthmatics while largely retaining the same gene activation profile for each species.
2020-08-10 | GSE135192 | GEO
Project description:BMPR2 mutation causes pulmonary arterial hypertension (PAH); ACE2 treatment can resolve established BMPR2-mediated PAH. The purpose of this study was to uncover the molecular mechanism behind this. Four groups: +/- ACE2 and +/- BMPR2 transgene, two arrays each, each array a pool of three animals.
2010-08-24 | E-GEOD-21583 | biostudies-arrayexpress
Project description:Background: Right ventricular (RV) and left ventricular (LV) myocardium differ in their response to pressure-overload hypertrophy (POH). In this report we use microarray and proteomic analyses to identify pathways modulated by LV-, and RV-POH in the immature heart. Methods: Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta (LV-POH; n=6). RV-POH was achieved by banding the pulmonary artery (n=6). Sham–control animals (SC; n=6 each) were sham-manipulated. Following 4 (LV-POH) and 6 weeks (RV-POH) recovery, the hearts were removed and matched sample RNA and proteins were isolated for microarray and proteomic analysis. Results: There was no difference in body weight in RV-, LV-POH vs. SC but there was a significant increase vs. SC in RV (3.2±0.8g vs. 1.2±0.3g; P<0.01) and LV weight (7.08±0.6g vs. 4.02±0.2g; P<0.01). Fractional area change (RV-POH) and shortening fraction (LV-POH) decreased significantly (23±6 vs. 47±6 and 21±4 vs.44±2, respectively, P<0.01). Microarray analysis demonstrated that LV-POH enriched pathways for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium and protein kinase-A signalling. RV-POH enriched pathways for cardiac oxidative phosphorylation. Proteomic analysis revealed 19 proteins were uniquely expressed in LV-POH vs. SC. Functional annotation clustering analysis indicated significant enrichment for the mitochondrion, cellular macromolecular complex assembly and oxidative phosphorylation. RV-POH had 15 uniquely expressed proteins vs. SC. Functional annotation clustering analysis indicated significant enrichment in structural constituents of muscle, cardiac muscle tissue development and calcium handling. Conclusion: Our results identify unique transcript and protein expression profiles in LV, RV-POH and provide new insight into the biological basis of ventricular specific hypertrophy. 3 different conditions: PAB-RV vs. Sham-control RV, PAB-RV [test] vs. PAB-LV [control], AOB-LV vs. Sham-control LV.
2011-06-24 | E-GEOD-30194 | biostudies-arrayexpress
Project description:Background: Adults with at least one copy of the minor allele in the rs6967330 SNP (AA/AG) in the rhinovirus (RV) receptor Cadherin related family member 3 gene (CDHR3), have a higher risk for CRS than those with two copies of the major allele (GG). Objective: To determine if the rs6967330 SNP increased the risk for acute exacerbations of chronic rhinosinusitis (AECRS) in adults and identify if their nasal cells showed a distinct pathophysiologic process activated by RV infection. Methods: We recruited adults with CRS (AG/AA,n=17; GG,n=37) and at baseline collected sinonasal outcome tests (SNOT-22), objective endoscopy scores, and nasal brushings for cells and RV viral detection. Subjects were contacted every two weeks for AECRS over one year, and if symptomatic this data was re-collected. To determine the effect of the rs6967330 SNP, air-liquid-interface (ALI) cultures were derived from nasal samples (AG/AA,n=19; GG,n=19). Cytokines and RNA transcriptome responses were measured 48 hours-post viral challenge with RV-A, RV-B, and RV-C. Results: During AECRS, adults with the AA/AG allele had 1.6x higher SNOT-22 scores, 2x higher endoscopic scores, and were 4x more likely to have RV infections during AECRS than those with the GG allele. (AA/AG) ALI cultures had significantly greater virus replication of RV-A (2.4x) and RV-C (3.5x) but not RV-B, higher levels of inflammatory cytokines, and significantly increased interferon-related pathways compared to (GG) ALI cultures. Conclusions: The minor allele in the rs6967330 SNP increases the risk for AECRS disease severity and is associated with an aberrant interferon-mediated inflammatory response to both RV-A and RV-C infections.
2024-09-12 | GSE270312 | GEO