Effect of mild respiratory SARS-CoV-2 infection on brainstem endothelial transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1005668 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25649138_1.fastq.gz | Fastqsanger.gz | |||
| SRR25649138_2.fastq.gz | Fastqsanger.gz | |||
| SRR25649139_1.fastq.gz | Fastqsanger.gz | |||
| SRR25649139_2.fastq.gz | Fastqsanger.gz | |||
| SRR25649140_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:To investigate the transcriptional response of brainstem endothelial cells to mild respiratory infection, 12-month-old male C57Bl/6 mice were intranasally inoculated with SARS-CoV-2 MA10 strain or with saline.
2023-08-25 | GSE240903 | GEO
Project description:The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has led to an unparalleled global health crisis. While the majority of COVID-19 patients present with mild respiratory issues, a subset of patients still develop severe symptoms and life-threatening complications. Notably, abnormal coagulation and thrombosis are significant contributors to mortality in severe COVID-19 patients. Therefore, this study stimulated aortic endothelial cells with SARS-Cov-2 S protein and performed transcriptome sequencing analysis.
2024-12-15 | GSE283771 | GEO
Project description:The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use 4 strains, time course, lungs
2011-08-31 | E-GEOD-23955 | biostudies-arrayexpress
Project description:In the initial process of COVID-19, SARS-CoV-2 infects respiratory epithelial cells and then transfers to other organs via the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin (VE-cadherin)-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in a COVID-19 patient’s lungs were decreased. CLDN5 overexpression or Fluvastatin treatment could rescue the SARS-CoV-2-induced respiratory endothelial barrier disruption. We therefore concluded that the downregulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a novel therapeutic strategy against COVID-19.
2022-09-22 | GSE196113 | GEO
Project description:The absence of a robust disease model currently hinders the evaluation of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV that results in mild-to-moderate disease has been utilized to describe the pathogenesis of this virus and for the evaluation of therapeutics, the inability to produce uniform disease with substantial virus replication complicates analysis in countermeasure studies. In an attempt to identify a more robust disease model, DPP4 sequences of various non-human primates were aligned. Modeling of the interactions between the receptor binding domain of MERS-CoV and its cognate receptor DPP4 predicted a "good fit" with complete conservation of all of the critical residues. To determine the feasibility of the marmoset as a MERS-CoV disease model, common marmosets were inoculated with MERS-CoV via combined intratracheal, intranasal, oral and ocular routes. Marmosets developed signs of moderate to severe illness with progressive serious to severe pneumonia. Progressive gross lesions were evident in animals necropsied at 3, 4 and 6 days post inoculation and two animals were euthanized during the study due to disease severity. This is the first description of a moderate-to-severe, with potentially lethality, disease model of MERS-CoV and as such will have utility for vaccine and other countermeasure efficacy evaluations in addition to further pathogenesis studies. Lung tissue samples were isolated and sequenced at 3, 4 and 6 days post inoculation. Two animals were euthanized during the study due to disease severity.
2014-06-10 | E-GEOD-55023 | biostudies-arrayexpress
Project description:In the initial process of COVID-19, SARS-CoV-2 infects respiratory epithelial cells and then transfers to other organs via the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin (VE-cadherin)-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in a COVID-19 patient’s lungs were decreased. CLDN5 overexpression or Fluvastatin treatment could rescue the SARS-CoV-2-induced respiratory endothelial barrier disruption. We therefore concluded that the downregulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a novel therapeutic strategy against COVID-19.
2022-09-22 | GSE206635 | GEO
Project description:For the assessment of host response dynamics to SARS-CoV and SARS-CoV-2 infections in human airway epithelial cells at ambient temperature corresponding to the upper or lower respiratory tract. We performed a temporal transcriptome analysis on human airway epithelial cell (hAEC) cultures infected with SARS-CoV and SARS-CoV-2, as well as uninfected hAEC cultures, incubated either at 33°C or 37°C. hAEC cultures were harvested at 24, 48 72, 96 hpi and processed for Bulk RNA Barcoding and sequencing (BRB-seq), which allows a rapid and sensitive genome-wide transcriptomic analysis in a highly multiplexed manner. Transcriptome data was obtained from a total of 7 biological donors for pairwise comparisons of SARS-CoV or SARS-CoV-2 virus-infected to unexposed hAEC cultures at respective time points and temperatures.
2020-11-27 | E-MTAB-9781 | biostudies-arrayexpress
Project description:A critical aspect of the mechanism of SARS-CoV-2 infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally. For this purpose, replication profiles of SARS-CoV-2 were analyzed in human respiratory organoids. All tested viruses, including Omicron variants, replicated efficiently in these organoids. Notably, all SARS-CoV-2 strains retained replication ability in TMPRSS2-gene knockout (KO) respiratory organoids, suggesting that TMPRSS2 is not essential for SARS-CoV-2 infection in human respiratory tissues. However, TMPRSS2-gene knockout significantly reduces the inhibitory effect of nafamostat, suggesting the advantage of TMPRSS2-utilizing ability for the SARS-CoV-2 infection in these organoids. Interestingly, Omicron variants regained the TMPRSS2-utilizing ability in recent subvariants. The basal infectivity would be supported mainly by cathepsins because the cathepsin inhibitor, EST, showed a significant inhibitory effect on infection with any SARS-CoV-2 strains, mainly when used with nafamostat. A supplementary contribution of other serine proteases was also suggested because the infection of the Delta variant was still inhibited partially by nafamostat in TMPRSS2 KO organoids. Thus, various proteases, including TMPRSS2, other serine proteases, and cathepsins, co-operatively contribute to SARS-CoV-2 infection significantly in the respiratory organoids. Thus, SARS-CoV-2 infection in the human respiratory tissues would be more complex than observed in cell lines or mice.
2024-11-20 | GSE279753 | GEO
Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.
2013-05-28 | E-GEOD-11704 | biostudies-arrayexpress
Project description:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts human health beyond acute infection. Myalgia and fatigue represent two of the most prevalent symptoms in post-COVID-19 syndrome. To determine the mechanisms underlying prolonged muscle symptoms, we characterized longitudinal histopathological and transcriptional changes of skeletal muscle after acute respiratory SARS-CoV-2 infection in a COVID-19 hamster model and compared them with respiratory influenza A virus (IAV) infection. Histopathological and bulk RNA sequencing analyses at 3, 30, and 60 days post infection (dpi) showed no evidence of direct viral invasion, inflammatory cell infiltration, or microthrombi in skeletal muscle, but myofiber atrophy was observed in the SARS-CoV-2 group at 60 dpi, accompanied by downregulation of myofiber genes, atrogenes, and cytoplasmic ribosomal protein genes, and upregulation of autophagy genes. There was persistent downregulation of genes involved in mitochondrial oxidative phosphorylation, fatty acid beta-oxidation, and tricarboxylic acid cycle in the SARS-CoV-2 but not the IAV group. Moreover, TNF-alpha/NF-kB and TGF-beta signaling pathways were differentially regulated in the SARS-CoV-2 group. Our findings suggest that persistent muscle symptoms after COVID-19 may be caused by muscle atrophy and energy metabolism suppression, and that the systemic inflammatory cytokine response may contribute, in part, to the skeletal muscle abnormalities.
2024-06-28 | GSE231910 | GEO