Ad26.COV2.S Prevents SARS-CoV-2 Induced Pathways of Inflammation and Thrombosis in Hamsters
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA807676 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18052641.fastq.gz | Fastqsanger.gz | |||
| SRR18052642.fastq.gz | Fastqsanger.gz | |||
| SRR18052643.fastq.gz | Fastqsanger.gz | |||
| SRR18052644.fastq.gz | Fastqsanger.gz | |||
| SRR18052645.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease, and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 challenge in hamsters stimulates myeloid and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, single-dose immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways such that the gene expression profiles of vaccinated hamsters are comparable to uninfected animals. Furthermore, we validated the protective efficacy of the Ad26.COV2.S against proinflammatory pathways and coagulation cascade in rhesus macaques by proteomics. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses. These data provide further insights into the mechanisms of Ad26.COV2.S based protection against severe COVID-19 in hamsters.
2022-03-26 | GSE196893 | GEO
Project description:Syrian golden hamsters were treated with TIP or control RNA and infected with SARS-CoV2, at 5 days post infection, RNA was extracted and RNAseq was performed, uninfected hamsters treated with TIP or Control RNA were used as controls.
2021-11-16 | GSE184447 | GEO
Project description:We tested if Brd2 inhibitor ABBV-744 could reduce SARS-CoV-2 infection in Syrian Hamsters. Three days post-infection, the lungs of hamsters were harvested and subjected to RNA-seq. Infected, but untreated, hamsters showed marked up-regulation of a number of genes including ISGs when compared to uninfected controls. In contrast, hamsters treated with ABBV-744 showed a down-regulation of ISG levels, confirming ABBV-744 activity. Thus, Brd2 inhibition can decrease SARS-CoV-2 infection in Syrian Hamsters.
2021-09-02 | GSE182994 | GEO
Project description:We report the application of bulk RNA sequencing technology for high-throughput profiling of SARS-CoV-2 infection in the lung of Syrian golden hamsters (Mesocricetus auratus).
2022-05-26 | GSE204696 | GEO
Project description:Vector-based SARS-CoV-2 vaccines such as AstraZeneca's ChAdOx1 nCoV-19 have been associated with vaccine-induced thrombosis (TTS/VITT). We studied ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson) and compared the vaccines using proteomics with mass spectrometric measurements. We could demonstrate that ChAdOx1 nCoV-19 contained significant amounts of human proteins in addition to adenoviral proteins. This was not the case for Ad26.COV2.S. Among the detected human proteins, proteasome subunits beta 1/delta and beta 5/MB1 were identified. In summary, both studied SARS-CoV-2 vaccines are markedly different concerning their content of contaminating proteins, which is most likely a determining factor for different frequencies of TTS/VITT after their application.
2023-05-04 | PXD027344 | Pride
Project description:The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details that underlie these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular and cellular pathways associated with SARS-CoV-2 pathogenesis, we performed transcriptomic analyses of bronchoalveolar lavage (BAL) samples and peripheral blood, and proteomics analyses of serum from infected rhesus macaques. We observed upregulation of macrophage signatures, complement cascade pathways, platelet activation, and markers of thrombosis in BAL and peripheral blood as well as extensive macrophage infiltrates in lung. These observations coincided with robust induction of interferon and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFa and NF-κB as well as downstream signaling pathways. These findings suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2 induced vascular disease. Our findings also suggest potential novel therapeutic targets for COVID-19 disease.
2020-10-20 | GSE156701 | GEO
Project description:Male sex belongs to one of the risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a host factor that contributes to worsened disease outcome in male hamsters. SARS-CoV-2 infection increases CYP19A1 transcription most prominently in the lungs of male animals, which correlates with reduced circulating testosterone and increased circulating estradiol levels. Dysregulated sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated sex hormone levels and was associated with improved lung function in male but not female animals compared to placebo controls. Whole-lung transcriptome analysis in letrozole treated versus placebo treated control groups revealed key pathways associated with improved lung health in males. To seek translation of these findings into humans, we analyzed autopsy-derived lung samples of COVID-19 cases from three independent study sites. We found that CYP19A1 transcription and protein expression is strongly elevated in the lungs of men who died with COVID-19 as compared to females or non-COVID-19 controls. Our findings highlight the role of the lung as a yet unrecognized but critical organ involved in metabolic responses against respiratory virus infections. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.
2022-01-21 | E-MTAB-11162 | biostudies-arrayexpress
Project description:SARS-CoV-2 can generate viral microRNAs (v-miRNAs) that target host gene expression. This study used small RNAseq to identify the v-miRNAs present in COVID-19 patients' nasopharyngeal swabs. The study identified a specific conserved v-miRNA sequence (CoV2-miR-O8) unique to SARS-CoV-2 that is highly present in COVID-19 patients' samples, interacts with Argonaute, and has features consistent with Dicer and Drosha generation. CoV2-miR-O8 is predicted to target specific human genes and can be detected by RTPCR assays in patients.
2023-12-11 | GSE230080 | GEO
Project description:This dataset looks at the transcriptome of in vitro-differentiated primary lung cells infected with SARS-CoV2. Some cells have been treated with the drug Enzalutamide.
2022-05-04 | E-MTAB-10687 | biostudies-arrayexpress