Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IL-9 exacerbates SARS-CoV2 infection and associated airway inflammation

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus diseases 2019 (COVID-19) and broncho-alveolar inflammation (Merad and Martin, 2020). IL-9 induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation (Temann et al., 1998). However, the role of IL-9 is not yet identified in SARS-CoV2 infection. Here we show that IL-9 promotes SARS-CoV2 infection and airway inflammation in K18-hACE2 transgenic (ACE2.Tg) mice, as IL-9 blockade reduces SARS-CoV2 infection and suppressed airway inflammation. Foxo1 is essential for the induction of IL-9 in helper T (Th) cells (Malik et al., 2017). While ACE2.Tg mice with Foxo1-deficiency in CD4+ T cells were performed to be resistant to SARS-CoV2 infection associated with reduced IL-9 production, exogenous IL-9 made Foxo1-deficient mice susceptible to SARS-CoV2 infection with increased airway inflammation. Collectively, we identify a mechanistic insight of IL-9-mediated regulation of antiviral and inflammatory pathways in SARS-CoV2 infection, and unravel a principle for the development of host-directed therapeutics to mitigate disease severity.

ORGANISM(S): Mus musculus

PROVIDER: GSE209550 | GEO | 2022/07/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

IL-13 decreases suceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo [Bulk RNA-seq]

Project description:Human airway epithelia (HAE) undergo inflammation-induced remodeling in chronic lung diseases such as asthma and chronic bronchitis. The role of type 2 inflammation-induced epithelial remodeling in SARS-CoV-2 infection and the course of COVID-19 is unclear, moreover, there is discrepancy in the literature regarding the potential benefit of treatments that modulate type 2 inflammation. We investigated the role of IL-13-induced inflammation on SARS-CoV-2 binding/entry, replication, and host response in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 in vivo. IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2- expressing ciliated cells rather than by neutralization in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened the severity of disease in mice in vivo; the effects were mediated by eicosanoid signaling and were abolished in mice deficient in the phospholipase A2 enzyme PLA2G2D. We conclude that IL-13-induced inflammation affects multiple steps of SARS-CoV-2-induced disease pathogenesis. Whereas IL-13-induced inflammation may be protective against initial infection at the airway epithelium, it enhances disease severity once infection progresses in vivo; blockade of IL-13 and/or eicosanoid signaling may be protective against progression to severe lung disease.

2024-06-26 | GSE249304 | GEO

MDM2 influences ACE2 stability and SARS-Cov2 uptake

Project description:The Angiotensin-converting enzyme 2 (ACE2) receptor is the central entry point for SARS-Cov2. Several SAR-Cov2 substrains have developed mutations in their spike protein to maximize their use of ACE2, e.g. to strengthen ACE2 binding for increased uptake or adapt to specific amino acid properties of ACE2 to cross the species barrier. But little is known about the effect of host regulators on ACE2 and subsequently their impact on SARS-Cov2 infection. Here we identify the E3 ligase MDM2 as a ACE2 modulator. The knockout of MDM2 induced a strong pro-viral effect specific for SARS-Cov2 and we could see the increase of ACE2 levels. This effect is likely dependent on the ubiquitination site Lysine 788, which MDM2 uses to induce proteasomal degradation of ACE2. Substituting this amino acid led to increased ACE2 levels and increased SARS-CoV2 infection facilitated by enhanced SARS-Cov2 uptake.

2023-09-08 | PXD040891 | Pride

A chemically-targetable transcription factor-chromatin remodeler interaction underlies SARS-CoV-2 susceptibility

Project description:Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and provides novel therapeutic targets. Here, we demonstrate that the mSWI/SNF chromatin remodeling complex promotes coronavirus infection and represents a host-directed therapeutic target. SMARCA4 catalytic activity is required for mSWI/SNF-driven chromatin accessibility at the ACE2 locus, which is essential for ACE2 expression and virus susceptibility. Recruitment of mSWI/SNF complexes to ACE2 is mediated by mSWI/SNF binding to the transcription factor, HNF1A, enabling complex occupancy and chromatin accessibility at sites containing high HNF1A motif density. Notably, small molecule inhibition of mSWI/SNF catalytic activity abrogates ACE2 expression confers resistance to SARS-CoV-2 variants and infection of primary human airway cells by 5-logs. These data highlight the role for mSWI/SNF-mediated chromatin remodeling activities in conferring SARS-CoV-2 susceptibility and identify a potential new class of inhibitors to combat COVID-19.

2022-10-11 | GSE186201 | GEO

ACE2 knockout hinders SARS-CoV-2 propagation in iPS cell-derived airway and alveolar epithelial cells

Project description:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to spread around the world with serious cases and deaths. It has also been suggested that different genetic variants in the human genome affect both the susceptibility to infection and severity of disease in COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) has been identified as a cell surface receptor for SARS-CoV and SARS-CoV-2 entry into cells. The construction of an experimental model system using human iPS cells would enable further studies of the association between viral characteristics and genetic variants. Airway and alveolar epithelial cells are cell types of the lung that express high levels of ACE2 and are suitable for in vitro infection experiments. Here, we show that human iPS cell-derived airway and alveolar epithelial cells are highly susceptible to viral infection of SARS-CoV-2. Using gene knockout with CRISPR-Cas9 in human iPS cells we demonstrate that ACE2 plays an essential role in the airway and alveolar epithelial cell entry of SARS-CoV-2 in vitro. Replication of SARS-CoV-2 was strongly suppressed in ACE2 knockout (KO) lung cells. Our model system based on human iPS cell-derived lung cells may be applied to understand the molecular biology regulating viral respiratory infection leading to potential therapeutic developments for COVID-19 and the prevention of future pandemics.

2024-08-21 | GSE275240 | GEO

Exploring the involvement of Adathoda vasica in hypoxia axis at the molecular level

Project description:The role of increased hypoxia has been identified for the many pathological features of SARS-CoV2, such as impaired immunity, airway hyper-inflammation, fibrosis, sepsis, and thrombosis. In this study, we tested the potential effect of Adhatoda Vasica (AV) aqueous extract, an ayurvedic anti-hypoxic, and anti-inflammatory medicine, on SARS-CoV2 infection using genome-wide expression approach. In this study, we did the genome-wide expression analysis of the lungs of mice treated with AV and compared them with transcriptome data of COVID19 patients. A meta-analysis of transcriptome profiles shows that AV may serve as a potential drug candidate to boost immune response and to prevent the transcriptional response elicited by SARS-CoV2 infection.

2020-09-30 | GSE156759 | GEO

SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

Project description:There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV-2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

2020-04-23 | GSE148829 | GEO

Selective Kinin Receptor B2 Antagonist Icatibant Reduces SARS-CoV-2 Replication in Primary Bronchial Epithelium Early

Project description:We provide evidence that the licensed drug icatibant, a selective antagonist of kinin B2 receptor interfering with the kinin-kallikrein system, has protective effects on primary airway epithelial cells (NHBE) during SARS-CoV-2 infection. Icatibant suppresses gene expression broadly, thereby reducing the expression of SARS-CoV-2 entry receptor ACE2 in vitro and in a murine airway inflammation model in vivo. Icatibant further impedes SARS-CoV-2 replication in NHBE and the release of infectious particles into supernatants.

2022-03-09 | GSE176405 | GEO

SUMOylation restrains the degradation of ACE2 through TOLLIP-mediated selective autophagy to facilitate the host susceptibility to SARS-CoV-2 infection

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.

2022-07-18 | GSE171130 | GEO

Promoter Capture Hi-C performed on A549 cells in a SARS-CoV2 infection timecourse

Project description:Here, A549 cells expressing the ACE2 receptor were infected with SARS-CoV2, and pCHi-C was performed at 0 (mock), 8 and 24 hours post-infection. This repository provides the raw pCHi-C sequence reads and downstream processed CHiCAGO data (Rds files).

2021-05-10 | GSE164533 | GEO

LC-MSMS of HEK 293T cells transfected with Flag-EV or Flag-ACE2

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Alongside investigation into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and pharmacological intervention of ACE2 SUMOylation blocks SARS-CoV-2 infection as well as viral infection-triggered immune responses. E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. TOLLIP depletion leads to the accumulation of ACE2 and the elevated SARS-CoV-2 infection. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.

2022-10-13 | PXD034168 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data