Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heterogeneous ribonucleoprotein interactions and impeded translational elongation in the respiratory tissue of SARS-CoV-2 pathology (RNA-Seq)

ABSTRACT: Translational regulation in in vivo tissue environments during viral pathogenesis has hardly been scrutinized due to the lack of tissue translatomes upon viral infection despite a number of the translatome studies on virus-infected cells cultured in vitro. We constructed the first temporal profile of lung translatomes during SARS-CoV-2 pathogenesis by applying ribosome profiling (Ribo-seq) to a severe COVID-19 mouse model. Unexpectedly, we observed gradual accumulations of non-canonical Ribo-seq reads representing hitherto-unidentified ribonucleoproteins (RNPs) that are likely involved in impeded translational elongation in the infected tissues. Contemporarily developing ribosome heterogeneity with prominently deviated 5S rRNP association supported the malfunction of elongating ribosomes. The analyses of canonical Riboseq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: attenuated translation for transcriptionally up-regulated genes including immune response genes and ribosome stalling on codons within transmembrane domain-coding regions. Our study elucidates hidden molecular features of gene regulation in vivo underlying SARS-CoV-2 pathogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE222251 | GEO | 2023/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Heterogeneous ribonucleoprotein interactions and impeded translational elongation in the respiratory tissue of SARS-CoV-2 pathology (Ribo-Seq)

Project description:Translational regulation in in vivo tissue environments during viral pathogenesis has hardly been scrutinized due to the lack of tissue translatomes upon viral infection despite a number of the translatome studies on virus-infected cells cultured in vitro. We constructed the first temporal profile of lung translatomes during SARS-CoV-2 pathogenesis by applying ribosome profiling (Ribo-seq) to a severe COVID-19 mouse model. Unexpectedly, we observed gradual accumulations of non-canonical Ribo-seq reads representing hitherto-unidentified ribonucleoproteins (RNPs) that are likely involved in impeded translational elongation in the infected tissues. Contemporarily developing ribosome heterogeneity with prominently deviated 5S rRNP association supported the malfunction of elongating ribosomes. The analyses of canonical Riboseq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: attenuated translation for transcriptionally up-regulated genes including immune response genes and ribosome stalling on codons within transmembrane domain-coding regions. Our study elucidates hidden molecular features of gene regulation in vivo underlying SARS-CoV-2 pathogenesis.

2023-12-01 | GSE222249 | GEO

Translational landscape of SARS-CoV-2 and infected cells

Project description:Purpose: Numerous viruses manipulate the host translation machinery and specifically block host mRNA translation. The goal of this study is to define the translational landscape of SARS-CoV-2 and SARS-CoV-2 infected cells using a combination of RNA-seq and ribo-seq approches, the latter being a powerful proxy for protein-level changes. Methods: Vero E6 and primary human bronchial epithelial cells were infected with SARS-CoV-2 at varying multiplicities of infection and followed throughout early and late phases of infection. Parallel samples were processed for RNA-seq and Ribo-seq. Sequencing reads were cleaned off of adapters and rRNAs. Reads were first mapped to the SARS-CoV-2 genome and then to the African green monkey and human genomes using STAR. Mapped reads were further annotated and processed using publicly available software and custom scripts deposited at Github. DE gene expression analysis was performed usign EdgeR. Gene set enrichment analysis was done using TcGSA. Results: We provide the transcriptomic and translatomic landscape of SARS-CoV-2-infected cells from multiple RNA-seq and ribo-seq libraries. We found that the robust transcriptional upregulation of numerous chemokines and cytokines are translationally blocked in SARS-CoV-2-infected cells. Conclusions: Our study represents the first detailed analysis of viral and host translational landscape in infected cells and demonstrate that translation of host mRNAs involved in innate immunity is specifically blocked. The optimized data analysis workflows reported here should provide a framework for translational profiling studies in other settings.

2020-11-23 | GSE158930 | GEO

E-GEOD-47962

Project description:SHAE004: SARS-CoV, SARS-dORF6 and SARS-BatSRBD infection of HAE cultures.

2025-01-24 | E-GEOD-47962 | ExpressionAtlas

In vivo structure and dynamics of the RNA genome of SARS-Cov-2

Project description:The SARS-CoV-2 coronavirus, which causes the COVID-19 pandemic, is one of the largest positive strand RNA viruses. Here we developed a simplified SPLASH assay and comprehensively mapped the in vivo RNA-RNA interactome of SARS-CoV-2 RNA during the viral life cycle. We observed canonical and alternative structures including 3’-UTR and 5’-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in cells and in virions. We provide the first evidence of comprehensive interactions between Transcription Regulating Sequences (TRS-L and TRS-Bs), which facilitate discontinuous transcription. In addition, we find alternative short and long distance arches around FSE, forming a “high-order pseudoknot” embedding FSE, which might help ribosome stalling at frameshift sites. We found that during packaging, SARS-CoV-2 genome RNA undergoes compaction while genome domains remain stable and genome cyclization is weakened. Our data provides a structural basis for the regulation of replication, discontinuous transcription and translational frameshifting describes dynamics on RNA structures during life cycle of SARS-CoV-2, and will help to develop antiviral strategies.

2021-08-29 | GSE164565 | GEO

Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

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

E-GEOD-150847

Project description:RNA-seq of SARS-CoV-2 infected lungs from mice sensitized for SARS-CoV-2 infection by Ad5-hACE2 transduction compared to non-sensitized mice

2021-03-22 | E-GEOD-150847 | ExpressionAtlas

E-GEOD-153970

Project description:Primary Human Airway Epithelial Cultures infected with SARS-CoV-2

2020-12-09 | E-GEOD-153970 | ExpressionAtlas

The PDZ-binding motif of SARS-CoV envelope protein is a determinant of viral pathogenesis

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

SARS-CoV-2 utilizes a multipronged strategy to suppress host protein synthesis

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 (COVID-19) pandemic. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. Here, we use RNA-sequencing and ribosome profiling along SARS-CoV-2 infection and comprehensively define the mechanisms that are utilized by SARS-CoV-2 to shutoff cellular protein synthesis. We show SARS-CoV-2 infection leads to a global reduction in translation but that viral transcripts are not preferentially translated. Instead, we reveal that infection leads to accelerated degradation of cytosolic cellular mRNAs which facilitates viral takeover of the mRNA pool in infected cells. Moreover, we show that the translation of transcripts whose expression is induced in response to infection, including innate immune genes, is impaired, implying infection prevents newly transcribed cellular mRNAs from accessing the ribosomes. Overall, our results uncover the multipronged strategy employed by SARS-CoV-2 to commandeer the translation machinery and to suppress host defenses.

2021-04-01 | GSE162323 | GEO

Bulk RNA Barcoding and sequencing (BRB-seq) of Mock, SARS-CoV, and SARS-CoV-2 infected human airway epithelial cell cultures at 33°C and 37°C

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data