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Insights into standards of care – dexamethasone and antibodies against COVID-19 in hamster models

ABSTRACT: We describe the cellular response to SARS-CoV-2 infections combined with antibody and/or dexamethasone treatment in Syrian and Roborovski dwarf hamsters

ORGANISM(S): Mesocricetus auratus Phodopus roborovskii

PROVIDER: GSE191080 | GEO | 2021/12/18

REPOSITORIES: GEO

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Insights into standards of care – dexamethasone and antibodies against COVID-19 in hamster models

Project description:Insights into standards of care – dexamethasone and antibodies against COVID-19 in hamster models

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RNA-Seq of hamster PDAC cancer (HapT1 cell line) biopsies taken after treatment with either an IgG control or new hamster specific anti-PD-L1 monoclonal antibody.

Project description:1. The experiment was performed to assess if the newly discovered Syrian hamster specific anti-PD-L1 antibody could induce a biologically relevant change in transcriptome profile in the tumours. This would confirm that the antibody has functional properties. In the larger picture, the Syrian Hamster model is favored over the mouse model for the development of vaccines and testing of oncolytic viruses/immunotherapies. This is because the model is semi permissive to virus replication compared to the mouse model. We can therefore more reliably assess the efficacy of oncolytic virotherapies, mainly oncolysis and promoter specific transgene expression. Moreover, we wanted to test potential improvements to treatment outcomes when combining oncolytic virotherapy and immune checkpoint blockade. However, there are not many commercially available research tools specific to the Syrian Hamster. This is why we developed an in vivo compatible immune checkpoint inhibitor so that we could assess the combination therapy in the Syrian hamster model. Lastly, we also wanted to validate if we could assess the efficacy of the immunotherapies using biopsies from hamsters to remove unnecessary use of animals. 2. To do this, we engrafted one PDAC tumours on the right flank of Syrian hamsters using 5 x10E+6 HapT1 cells grown in culture. When tumours reached 4-5mm in diameter, the hamsters were injected intraperitoneally with either 300ug of IgG2a control or anti-PD-L1 (clone;11B12-1). Hamsters were treated 8 times and a tumour biopsy was taken one day before the last treatment. The biopsy was immediately stored in RNA-later until extraction with RNA mini kit (Qiagen).

2023-01-30 | E-MTAB-12297 | biostudies-arrayexpress

Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance

Project description:RNA sequencing was performed on Golden Syrian hamster fat tissue depots from hamsters inoculated with SARS-CoV-2 in PBS or PBS only

2021-09-29 | GSE183714 | GEO

Changes in the gene expression in the inferior colliculus of the sound stimulated both control Syrian hamsters and the strain GASH:Sal.

Project description:Using microarray analyses and subsequent verification by RT-PCR, we studied the changes in gene expression in the inferior colliculus after an ictal event in one models of audiogenic epilepsy, genetic audiogenic seizure hamster (GASH:Sal). GASH:Sal, a hamster strain developed at the University of Salamanca, exhibits genetic audiogenic epilepsy similar to human Grand Mal epilepsy. GASH:Sal shows an autosomal recessive inheritance for susceptibility to audiogenic seizures, which manifest more severely in young animals; the seizure severity progressively declines with age. Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were subjected to auditory stimulation, and 60 minutes after stimulation, the inferior colliculi were collected. As a control, intact Wistar rats and Syrian hamsters were subjected to identical stimulation and tissue preparation protocols to those performed on the experimental animals. A total of 24 animals were used in this study according to the following distribution: 12 control Syrian hamsters (Mesocricetus auratus) and 12 GASH:Sal at 16 weeks of age and a body weight of approximately 60 g. Six animals Syrian and GASH:Sal hamsters, respectively, were exposed to auditory stimulation, and 60 min after the seizures, we harvested the IC for all gene expression analyses (stimulated Syrian hamsters and stimulated GASH:Sal hamsters). As controls, other six animals Syrian and GASH:Sal hamsters, respectively, were not exposed to the same stimulation (Syrian hamsters and GASH:Sal hamsters).

2015-12-31 | E-GEOD-74043 | biostudies-arrayexpress

Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

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.

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Quantitative proteomics analysis of COVID-19 infected hamster lung tissue

Project description:The mechanistic interplay between SARS-CoV-2 infection, inflammation, and oxygen homeostasis is not well defined. Here we show that the hypoxia-inducible factor (HIF-1α) transcriptional pathway is activated, perhaps due to a lack of oxygen or an accumulation of mitochondrial reactive oxygen species (ROS) in the lungs of adult Syrian hamsters infected with SARS-CoV-2. Prominent nuclear localization of HIF-1 and increased expression of HIF-1α target proteins, including glucose transporter 1 (Glut1), lactate dehydrogenase (LDH), and pyruvate dehydrogenase kinase-1 (PDK1), were observed in areas of lung consolidation filled with infiltrating monocytes/macrophages. Upregulation of these HIF-1α target proteins was accompanied by a rise in glycolysis as measured by extracellular acidification rate (ECAR) in lung homogenates. A concomitant marginal reduction in mitochondrial respiration was also observed as seen by a partial loss of oxygen consumption rates (OCR) in both coupled and uncoupled states of respiration in isolated mitochondrial fractions of SARS-CoV-2 infected hamster lungs. Proteomics analysis revealed specific deficits in the mitochondrial ATP synthase (Atp5a1) within complex V and in the ATP/ADP translocase (Slc25a4). The activation of HIF-1 in inflammatory macrophages may also drive proinflammatory cytokines production, complement activation, and oxidative stress in infected lungs. Together, these findings support a role for HIF-1 as a central mediator of the metabolic reprogramming, inflammation, and mitochondrial dysfunction associated with COVID-19 disease.

2023-03-10 | PXD036862 | Pride

RNA-sequencing identifies the activation of IFN-dependent and IFN-independent pathways in the lungs of hamsters treated with NanoSTING

Project description:To investigate the impact of intranasal NanoSTING administration on the lungs of Syrian Golden hamsters (Mesocricetus auratus)

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Analysis of the antiviral activity of TIP against SARS-CoV2 in Mesocricetus auratus

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

A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants

Project description:We describe the cellular response to SARS-CoV-2 infections in Syrian hamsters previously immunized with mRNA, Adenovirus, and life-attenuated virus vaccines.

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Bulk RNA sequencing in SARS-CoV-2-infected hamsters

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

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