Cytokines and lipid mediators of inflammation in lungs of SARS-CoV-2 infected mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205014 | GEO | 2022/05/30
REPOSITORIES: GEO
Similar Datasets
Project description:To investigated neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan early strain) in K18-hACE2 mice.
2023-03-08 | GSE214516 | GEO
Project description:We evaluate heterozygous transgenic mice expressing human ACE2 receptor driven by the epithelial cell promoter cytokeratin-18 promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of K18-hACE2 mice with SARS-CoV-2 results in high levels of infection in the lung parenchyma with spread to other organs.
2020-07-29 | GSE154104 | GEO
Project description:Coronavirus disease 19 (COVID-19) is the clinical manifestation of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. A hallmark of COVID-19 is a lung inflammation characterized by an abundant leukocyte infiltrate, elevated levels of cytokines/chemokines, lipid mediators of inflammation (LMI) and microthrombotic events. Animal models are useful for understanding the pathophysiological events leading to COVID-19. One such animal model is the K18-ACE2 transgenic mice. Despite their importance in inflammation, the study of LMI in lung of SARS-CoV-2 infected K18-ACE2 mice has yet to be studied to our knowledge. Using tandem mass spectrometry, the lung lipidome at different time points of infection was analyzed. Significantly increased LMI included N-oleoyl-serine, N-linoleoyl-glycine, N-oleoyl-alanine, 1/2-linoleoyl-glycerol, 1/2-docosahexaenoyl-glycerol and 12-hydroxy-eicosapenatenoic acid. The levels of prostaglandin (PG) E1, PGF2α, stearoyl-ethanolamide and linoleoyl-ethanolamide were found to be significantly reduced relative to mock-infected mice. Other LMI were present at similar levels (or undetected) in both uninfected and infected mouse lungs. In parallel to LMI measures, transcriptomic and cytokine/chemokine profiling were performed. Viral replication was robust with maximal lung viral loads detected on days 2-3 post-infection. Lung histology revealed leukocyte infiltration starting on day 3 post-infection, which correlated with the presence of high concentrations of several chemokines/cytokines. At early times post-infection, the plasma of infected mice contained highly elevated concentration of D-dimers suggestive of blood clot formation/dissolution. In support, the presence of blood clots in the lung vasculature was observed during infection. RNA-Seq analysis of lung tissues indicate that SARS-CoV-2 infection results in the progressive modulation of several hundred genes, including several inflammatory mediators and genes related to the interferons. Analysis of the lung lipidome indicated modest, yet significant modulation of a minority of lipids. In summary, our study suggests that SARS-CoV-2 infection in humans and mice share common features, such as elevated levels of chemokines in lungs, leukocyte infiltration and increased levels of circulating D-dimers. However, the K18-ACE2 mouse model highlight major differences in terms of LMI being produced in response to SARS-CoV-2 infection. The potential reasons and impact of these differences on the pathology and therapeutic strategies to be employed to treat severe COVID-19 are discussed.
| S-EPMC9264370 | biostudies-literature
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
Project description:The spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates binding to the ACE2 receptor and subsequent membrane fusion. It exists in a range of conformations, including a closed state unable to bind the ACE2 receptor, and an open state that does so but displays more exposed antigenic surface. Spikes of variants of concern (VOCs) acquired amino acid changes linked to different opening probabilities, increased SARS-CoV-2 virulence and immune evasion. Here, using hydrogen-deuterium exchange mass spectrometry (HDX-MS), we analyzed the spike of the original Wuhan isolate, G614 mutant, spike of alpha, beta, delta and omicron VOCs and the isolated ancestral receptor binding domain (RBD) - in apo state and in complex with the ACE2 receptor. We identified changes in spike dynamics that we associated with the transition from closed to open conformation, to ACE2 binding, and to specific mutations in VOCs. We show that the RBD-associated subdomain plays a role in spike opening, whereas the NTD acts as a hotspot of conformational divergence of VOC spikes driving immune evasion. Alpha, beta and delta spikes assume predominantly open conformations and a strong ACE2 binding increases the dynamics of their core helices, priming spikes for fusion. Conversely, substitutions in omicron spike lead to predominantly binding-incompetent closed conformations, presumably enabling it to escape antibodies. At the same time, its core helices show characteristics of being pre-primed for fusion even in the absence of ACE2. These data inform on SARS-CoV-2 evolution and omicron variant emergence.
2023-03-15 | PXD039760 | Pride
Project description:The spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates binding to the ACE2 receptor and subsequent membrane fusion. It exists in a range of conformations, including a closed state unable to bind the ACE2 receptor, and an open state that does so but displays more exposed antigenic surface. Spikes of variants of concern (VOCs) acquired amino acid changes linked to different opening probabilities, increased SARS-CoV-2 virulence and immune evasion. Here, using hydrogen-deuterium exchange mass spectrometry (HDX-MS), we analyzed the spike of the original Wuhan isolate, G614 mutant, spike of alpha, beta, delta and omicron VOCs and the isolated ancestral receptor binding domain (RBD) - in apo state and in complex with the ACE2 receptor. We identified changes in spike dynamics that we associated with the transition from closed to open conformation, to ACE2 binding, and to specific mutations in VOCs. We show that the RBD-associated subdomain plays a role in spike opening, whereas the NTD acts as a hotspot of conformational divergence of VOC spikes driving immune evasion. Alpha, beta and delta spikes assume predominantly open conformations and a strong ACE2 binding increases the dynamics of their core helices, priming spikes for fusion. Conversely, substitutions in omicron spike lead to predominantly binding-incompetent closed conformations, presumably enabling it to escape antibodies. At the same time, its core helices show characteristics of being pre-primed for fusion even in the absence of ACE2. These data inform on SARS-CoV-2 evolution and omicron variant emergence.
2023-03-15 | PXD039762 | Pride
Project description:Age-matched K18-hACE2 transgenic mice were passively transferred with human COVID-19 mRNA post-vaccination (post-vac) sera followed by the lethal challenge with different SARS-CoV-2 viruses via intranasal route, including (1) New York-PV09158/2020 (NY) of lineage B.1.3 bearing 614G, (2) Kappa (B.1.617.1) and (3) Delta (B.1.617.2). Mouse lungs were harvested on 5 days post infection (dpi). Total RNA was extracted using QIAgen RNeasy Plus Mini Kit and was reverse transcribed using the High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific). Resultant cDNA was used as the template along with RT2 SYBR Green ROX qPCR Mastermix (Qiagen) to perform RT² Profiler™ PCR Array Mouse Hypoxia Signaling Pathway (Qiagen) real-time PCR in Stratagene MX3000p qPCR system.
2022-11-21 | GSE193839 | GEO
Project description:Recent epidemiological studies suggest that individuals with Down syndrome are more susceptible to SARS-CoV-2 infection and have higher rates of hospitalization and mortality than the general population. However, the main drivers behind these disparate health outcomes remain unknown. Herein we performed experimental infections with SARS-CoV-2 in a well-established mouse model of Down syndrome, Dp(16)1Yey/+;Tg(K18-ACE2)2Prlmn/+ (abbreviated as Dp16;ACE2). We observed similar SARS-CoV-2 replication kinetics and dissemination in the primary and secondary organs between mice with and without Down syndrome (i.e., Dp16;ACE2 and ACE2), suggesting that both groups have similar susceptibilities to SARS-CoV-2 infection. However, Down syndrome mice exhibited more severe disease as defined by clinical features including symptoms, weight loss, pulmonary function, and survival of mice. We found that increased disease severity in Down syndrome mice could not be attributed solely to increased infectivity or a more dramatic pro-inflammatory response to infection. Rather, results from RNA sequencing suggested that differences in expression of genes from other physiological pathways such as deficient oxidative phosphorylation, cardiopulmonary dysfunction and deficient mucociliary clearance in the lungs may also contribute to heightened disease severity and mortality in Down syndrome mice following SARS-CoV-2 infection.
2024-03-04 | GSE260583 | GEO
Project description:The SARS-CoV-2 Delta variant is more contagious than WT and causes severe symptoms.To understand the elevated fusogenicity of Delta, we used LC-MS/MS to characterize the site specific N-linked glycan of spike protein in SARS-CoV-2 Delta variant virions.The glycan analysis revealed increased oligomannose-type glycosylation of native Delta spike over that of the Wuhan-Hu-1 spike.
2023-05-10 | PXD033342 | Pride
Project description:Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. We studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies, in surviving mice up to 4 months post-acute infection, revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients.
2024-04-15 | GSE260625 | GEO