EGAS00001004489-sc-2022-12-02T14:07:17Z - samples
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ABSTRACT:
PROVIDER: EGAD00001009773 | EGA |
REPOSITORIES: EGA
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Project description:A recombinant SARS-CoV lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major virulence determinant in vivo. Elimination of SARS-CoV E protein PBM by using reverse genetics led to attenuated viruses (SARS-CoV-mutPBM) and to a reduction in the deleterious exacerbate immune response triggered during infection with the parental virus (SARS-CoV-wt). Cellular protein syntenin bound E protein PBM during SARS-CoV infection. Syntenin activates p38 MAPK leading to overexpression of inflammatory cytokines, and we have shown that active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM (SARS-CoV-mutPBM) as compared with the parental virus (SARS-CoV-wt), leading to a decreased expression of inflammatory cytokines and to viral attenuation. Therefore, E protein PBM is a virulence factor that activates pathogenic immune response most likely by using syntenin as a mediator of p38 MAPK induced inflammation. Three biological replicates were independently hybridized (one channel per slide) for each sample type (SARS-CoV-wt, SARS-CoV-mutPBM, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)
2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress
Project description:Healthcare workers were recruited at St Bartholomew’s Hospital, London, UK in the week of lockdown in the United Kingdom (between 23rd and 31st March 2020). Participants underwent weekly evaluation using a questionnaire and biological sample collection (including serological assays) for up to 16 weeks when attending for work and self-declared as fit to attend work at each visit, with further follow up samples collected at 24 weeks. Blood RNA sequencing data was to be used to identify host-response biomarkers of early SARS-CoV-2 infection, to evaluate existing blood transcriptomic signatures of viral infection, and to describe the underlying biology during SARS-CoV-2 infection. This submission includes a total of 172 blood RNA samples from 99 participants. Of these, 114 samples (including 16 convalescent samples collected 6 months after infection) were obtained from 41 SARS-CoV-2 cases, with the remaining 58 from uninfected controls. Participants with available blood RNA samples who had PCR-confirmed SARS-CoV-2 infection during follow-up were included as ‘cases’. Those without evidence of SARS-CoV-2 infection on nasopharyngeal swabs and who remained seronegative by both Euroimmun anti S1 spike protein and Roche anti nucleocapsid protein throughout follow-up were included as uninfected controls. ‘Cases’ include all available RNA samples, including convalescent samples at week 24 of follow-up for a subset of participants. For uninfected controls, we included baseline samples only. Sample class denotes weekly interval to positive SARS-CoV-2 PCR; non-infected controls (NIC); convalescent samples (Conv)_.
2021-07-07 | E-MTAB-10022 | biostudies-arrayexpress
Project description:The SARS-CoV-2 virus is continuously evolving, with appearance of new variants characterized by multiple genomic mutations, some of which can affect functional properties, including infectivity, interactions with host immunity, and disease severity. The rapid spread of new SARS-CoV-2 variants has highlighted the urgency to trace the virus evolution, to help limit its diffusion, and to assess effectiveness of containment strategies. We propose here a PCR-based rapid, sensitive and low-cost allelic discrimination assay panel for the identification of SARS-CoV-2 genotypes, useful for detection in different sample types, such as nasopharyngeal swabs and wastewater. The tests carried out demonstrate that this in-house assay, whose results were confirmed by SARS-CoV-2 whole-genome sequencing, can detect variations in up to 10 viral genome positions at once and is specific and highly sensitive for identification of all tested SARS-CoV-2 clades, even in the case of samples very diluted and of poor quality, particularly difficult to analyze.
2022-06-03 | E-MTAB-11261 | biostudies-arrayexpress
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:Background: Type I interferons (IFNs) are essential to the clearance of viral diseases, in part by initiating upregulation of IFN regulated genes (IRGs). A clear distinction between genes upregulated directly by virus and genes upregulated by secondary IFN production has not been made. Here we investigated the genes regulated by IFN-a2b compared to the genes regulated by SARS-CoV infection in ferrets. Methods: We characterized early host immune responses in peripheral blood and lung necropsies of ferrets injected with IFN-a2b or infected with SARS-CoV/Tor 2 strain, using microarray analysis on the Affymetrix platform. Results: We identified a common IRG signature that was upregulated in both SARS-CoV infected ferrets as well as in ferrets injected with IFN-a2b. We also identified unique patterns of gene expression for leukocyte activation, cell adhesion and complement pathways between IFN-a2b injection and SARS-CoV infection. Conclusions: Our results define the effects of IFN-a2b on the immune system of ferrets highlighting genes regulated by IFN during SARS-CoV infection. We have shown the similarities and differences of top funcional gene groups as well as pathways that play key roles in early immune responses in ferrets in response to IFN-a2b or SARS-CoV. Key words: ferret, gene expression, SARS, interferon. Keywords: time course In experiments with IFN-a2b, for peripheral blood, 15 ferrets were randomly allocated to 3 groups: Day 0, 5 ferrets (no IFN injection), day 1, 6 ferrets (injected), and day 2, 4 ferrets (injected). For lung necropsies of injected ferrets with IFN-a2b, we used 12 ferrets in 3 groups: 4 ferrets, day 0 (no IFN injection), 4 ferrets, day 1 (injected) and 4 ferrets, day 2 (injected). Experimental groups for SARS-CoV infection was as follows: For peripheral blood, 3 and 4 ferrets for day 0 (no infection) and day 2 (infection) respectively. For lung neceropsies, a total of 9 ferrets in 3 groups, each with 3 replicates for day 0 (no infection), day 1 (infection) and day 2 (infection).
2010-12-01 | E-GEOD-22581 | biostudies-arrayexpress
Project description:SARS-CoV-2 infection leads to vastly divergent and heterogeneous clinical outcomes ranging from asymptomatic to fatal disease. Co-morbidities, sex, age, and host genetics together with vaccine status are known to affect disease severity. However, how the inflammatory milieu of the lung at the time of SARS-CoV-2 infection impacts control of the virus remains less well understood. Here, we identify key innate immune pathways required to limit viral replication, including the pro-inflammatory cytokine TNFα. Moreover, we demonstrate here that recent immune events in the lung proximal to the time of SARS-CoV-2 exposure can drastically impact viral control. A diverse set of pulmonary inflammatory stimuli, ranging from prior resolved respiratory infections of S. aureus or influenza, ongoing M. tuberculosis infection, or ovalbumin/alum-induced asthma to administration of defined TLR ligands and recombinant cytokines, resulted in an antiviral state that potently limited SARS-CoV-2 replication. In addition to type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 very effectively conditioned the lung for enhanced viral control. Collectively, our work reveals that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and indicates that the recent and momentary pulmonary inflammatory tone during SARS-CoV-2 exposure may contribute to the population-wide variability in COVID-19 disease outcomes.
2024-05-30 | GSE268196 | GEO
Project description:COVID-19 pandemic caused by SARS-CoV-2 is far from getting over because of the emergence of different SARS-CoV-2 variants even though vaccination against SARS-CoV-2 is ongoing. Variant specific mechanistic understanding of host-viral interaction will be required to design novel anti-viral therapeutics. N6-methyladenosine modification (m6A) which is one of the abundant cellular RNA modifications regulates key processes in RNA metabolism during stress response. We observed different SARS-CoV-2 variants during infection causes global loss of m6A in cellular RNA whereas m6A modification was detected abundantly in viral RNA. The loss of m6A in cellular RNAs was more drastic in B.1 and B1.1.7 strains and the main m6A methyltransferase METTL3 shows cytoplasmic localization post-infection. In B1.351 variant effect on METTL3 localization and loss of m6A was less pronounced compared to B.1 and B1.1.7 variants. Gene expression profile suggested changes in RNA catabolism-related pathways including key genes related to m6A readers and erasers during SARS-CoV-2 infection. Genes with m6A peaks were more susceptible to down-regulation during viral infection. Inhibition of export protein XPO1 during infection results in restoration of METTL3 nuclear localization and reduction in viral infection in cell culture suggesting XPO1 inhibition could be an effective therapeutic option for SARS-CoV-2.
2023-02-07 | GSE188477 | GEO
Project description:The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remain unclear. Here, we combine a multiomics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.
2022-01-17 | GSE193708 | GEO
Project description:The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify macrophages to have elevated expression of IFI27 in areas of infection.
2024-01-28 | GSE253474 | GEO
Project description:The worldwide spread of severe acute respiratory syndrome-related coronavirus-2 (SARS- CoV-2) caused an urgent need for an in-depth understanding of virus-host interactions. Here, we dissected the dynamics of virus replication and the host cell transcriptional response to SARS-CoV-2 infection at a systems level by combining time-resolved RNA sequencing with mathematical modeling. We observed an immediate transcriptional activation of inflammatory pathways linked to the anti-viral response followed by increased expression of genes involved in ribosome and mitochondria function, thus hinting at rapid alterations in protein production and cellular energy supply. At later stages, metabolic processes, in particular those related to xenobiotic metabolism, were downregulated. To gain a deeper understanding of the underlying transcriptional dynamics, we developed an ODE model of SARS-CoV-2 infection and replication. Mathematical modeling of SARS-CoV-2 replication suggested a strong inhibitory effect of SARS-CoV-2 proteins on the anti-viral response and a large excess of virus transcripts over the translation capacity. Our study provides insights into the sequence of SARS-CoV-2 virus-host interactions and facilitates the identification of druggable host pathways supporting virus replication.
2022-11-10 | GSE217504 | GEO