Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens Macaca mulatta Macaca fascicularis

PROVIDER: GSE148829 | GEO | 2020/04/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

HIV infection drives interferon signaling within intestinal SARS-CoV-2 susceptible target cells

Project description:SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed single-cell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2–infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.

2021-08-18 | GSE181877 | GEO

Targeting Transcriptional Regulation of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2

Project description:SARS-CoV-2, the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity. Several studies, including one employing a large epidemiological cohort, suggested that blocking androgen signaling is protective against COVID-19. Here, we demonstrate that androgens regulate the expression of ACE2, TMPRSS2, and androgen receptor (AR) in subsets of lung epithelial cells. AR levels are markedly elevated in males relative to females greater than 70 years of age. In males greater than 70 years old, smoking was associated with elevated levels of AR and ACE2 in lung epithelial cells. Transcriptional repression of the AR enhancesome with AR or bromodomain and extraterminal domain (BET) antagonists inhibited SARS-CoV-2 infection in vitro. Taken together, these studies support further investigation of transcriptional inhibition of critical host factors in the treatment or prevention of COVID-19. These mouse data are part of a larger investigation (data not provided here) targeting the transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

2020-11-30 | GSE159576 | GEO

ACE2 independent SARS-CoV-2 infection of a human lung cell line

Project description:In a screen of human upper airway cell lines, we identified the H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite no evidence of ACE2 or TMPRSS2 expression. Temporally resolved transcriptomic and proteomic profiling of H522 cells revealed consistent alterations in the antiviral host cell response, including marked activation of type-I interferon signaling. Focused chemical screens point to important roles for clathrin-mediated endocytosis and endosomal cathepsins in SARS-CoV-2 infection of H522 cells. The natural permissiveness of H522 cells to SARS-CoV-2 infection despite no requirement for ACE2 implies the utilization of an alternative receptor and viral entry mechanism which may have important implications for SARS-CoV-2 pathogenesis in humans.

2022-03-07 | PXD023754 | Pride

Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2

Project description:Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity pose the urgency for developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction is a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2 and protect the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates their deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protected hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercept the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and show comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as broad-spectrum protectant against existing and emerging virus variants.

2024-01-13 | GSE249987 | GEO

A gene locus that controls expression of ACE2 in virus infection

Project description:The SARS-CoV-2 pandemic has resulted in widespread morbidity and mortality globally, but with widely variable outcomes. The development of severe disease and mortality is higher in older individuals, males and those with other co-morbidities, and may vary across ethnic groups. However, so far, no host genetic factor has been clearly associated with susceptibility and development of severe disease. To understand the impact of host genetics on expression of ACE2 (SARS-CoV-2 receptor) during RNA virus infection we performed a GWAS for ACE2 expression in HCV-infected liver tissue from 195 individuals. We discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. ACE2 expression was regulated additionally by age, with a subsidiary effect of co-morbidity. The IFNL locus controlled expression of a gene network incorporating many well-known interferon-stimulated genes which anti-correlated with ACE2 transcript levels. The same anti-correlation was found in the gastrointestinal tract, a site of SARS-CoV-2 replication where inflammation driven interferon-stimulated genes are negatively correlated with ACE2 expression. The interferon dependent regulation of ACE2 was identified in a murine model of SARS-CoV-1 suggesting conserved regulation of ACE2 across species. Polymorphisms in the IFNL region, as well as age, may impact not only on classical antiviral responses but also on ACE2 with potential consequences for clinical outcomes in distinct ethnic groups and with implications for therapeutic interventions.

2020-04-30 | GSE149601 | GEO

RNAseq analyses in HEK293T-ACE2 cells infected with SARS-CoV-2 (VOC Delta, 24hours) vs untreated cells

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

ACE2-independent SARS-CoV-2 virus entry through cell surface GRP78 on monocytes - evidence from a translational clinical and experimental approach

Project description:SARS-CoV-2 infects host cells via an ACE2/TMPRSS2 entry mechanism. Monocytes and macrophages, which play a key role during severe COVID-19 express only low or no ACE2, suggesting alternative entry mechanisms in these cells. In silico analyses predicted GRP78, which is constitutively expressed on monocytes and macrophages, to be a potential candidate receptor for SARS-CoV-2 virus entry. To confirm the hypothesis, we conducted high-throughput RNA sequence to characterize the role of GRP78 in monocytes function in COVID-19 patients

2023-12-13 | GSE245922 | GEO

Attenuation of SARS-CoV-2 Infection by Losartan in Human Kidney Organoids

Project description:COVID-19 associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. It is unclear how susceptible human kidneys are to direct SARS-CoV-2 infection and whether pharmacologic manipulation of the renin-angiotensin II signaling (RAS) pathway modulates this susceptibility. Using induced pluripotent stem cell derived kidney organoids, SARS-CoV-1, SARS-CoV-2 and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily amongst proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in COVID-19 patients, inhibited angiotensin II mediated internalization of ACE2, upregulated interferon stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.

2022-01-23 | GSE149687 | GEO

Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

Project description:Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.

2021-04-18 | GSE166990 | GEO

Single-cell transcriptomics of mouse small intestinal epithelial cells and intraepithelial lymphocytes

Project description:The goal of this study is to obtain single-cell based transcription data in different intestinal epithelial cell sub-populations. Specifically, we were interested in determining which intestinal epithelial cell subsets express ACE2, the SARS-CoV-2 receptor, and TMPRSS2, a serine protease that facilitates viral spike protein cleavage and virus entry.

2020-05-06 | GSE149907 | GEO

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