Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative Host-Coronavirus Protein Interaction Networks Reveal Pan-Viral Disease Mechanisms

ABSTRACT: Abstract: The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, has highlighted emergent viruses as significant threats to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. We find that proteins often do not change localization across viruses but their sequence divergence dictates differences in host interactions. Functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryoEM. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms (IL-17 regulation) and drug treatments (sigma-1 receptor ligands) that merit further molecular and clinical study.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Nevan Krogan

PROVIDER: MSV000086489 | MassIVE | Thu Nov 19 16:15:00 GMT 2020

SECONDARY ACCESSION(S): PXD021588

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Comparative Host-Coronavirus Protein Interaction Networks Reveal Pan-Viral Disease Mechanisms

Project description:Abstract: The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, has highlighted emergent viruses as significant threats to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. We find that proteins often do not change localization across viruses but their sequence divergence dictates differences in host interactions. Functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryoEM. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms (IL-17 regulation) and drug treatments (sigma-1 receptor ligands) that merit further molecular and clinical study.

2020-10-16 | PXD021588 | Pride

RNA-Seq of Human iPSC-cardiomyocytes infected with SARS-CoV-2

Project description:Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood.

2020-06-19 | GSE150392 | GEO

RNA sequencing of SARS-CoV and SARS-CoV-2 N proteins expressing cell lines

Project description:SARS-CoV and SARS-CoV-2, the causative agents of severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), are genetically related positive-sense RNA viruses that may cause similar pathophysiology. Despite host could activate interferon responses upon coronaviral infection to suppress virus replication, both SARS-CoV and SARS-CoV-2 have evolved strategies to inhibit interferon response. Here, we constructed SARS-CoV and SARS-CoV-2 N proteins expressing cell lines (HEK293T-N and HEK293T-2N) and performed RNA sequencing analysis, showing that both SARS-CoV-2 and SARS-CoV N proteins could inhibit expression of early growth response gene 1 (EGR1) to suppress interferon response. Moreover, EGR1 could degrade N proteins of SARS-CoV and SARS-CoV-2 in a lysosome-dependent manner, and inhibit viral replication of SARS-CoV-2. Our findings revealed the important role of EGR1 in host innate immune response against SARS-CoV and SARS-CoV-2, which would contribute to understanding the pathogenesis of human coronaviruses and development of antiviral therapies. In addition, we demonstrated that both N proteins could upregulate expression of nervous development-related genes, which may be associated with the neurological symptoms of COVID-19 and SARS patients.

2023-08-20 | GSE189706 | GEO

Genes and transposons expression profiling of wild-type Bone Marrow Derived Macrophages (BMDMs) after VSV and HSV infection.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging and highly pathogenic coronavirus that causes coronavirus disease (COVID-19), and might even lead to death. The long terminal repeat of the endogenous retrovirus (LTR ERVs), a type of mammalian genome elements derived from ancient viruses which infected the host and now accounts for 8% of human genome, are implicated in multi viral pathogenesis and host immune responses. However, their expression patterns and functions during SARS-CoV-2 infection still remain to be uncover. We first identified that SARS-CoV-2 infection could upregualted the expression of TEs and ERVs from the published RNA-seq data. Then in this study, we also conducted the genome-wide analysis of ERVs from wild-type mice Bone Marrow Derived Macrophages (BMDMs) after VSV and HSV infection. Collectively, these results provides the first glimpse into the expression patterns and potentail roles of ERVs after viral infection, and would serve as a valuable resource for future studies on SARS-CoV-2 infection and pathogenesis.

2023-11-30 | GSE244322 | GEO

m6A modification in SARS-CoV-2 virus regulates host cell innate immune response

Project description:It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlying molecular mechanism. RNA modification landscape of SARS-CoV-2 and its functional relevance to host cell innate immune response remain unknown. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigated m6A modification of SARS-CoV-2 gene in regulating host cell innate immune response. Our data showed that SARS-CoV-2 virus has m6A modification enriched in 3' region of the viral genome. We also found that host cell m6A methyltransferase METTL3 depletion reduced viral load in infected cells, decreased m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increased RIG-1 binding and subsequently enhanced downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in severe COVID-19 patients. These findings will aid to understand the COVID-19 pathogenesis and help in designing future studies of regulating innate immunity for COVID-19 treatment.

2021-04-27 | GSE167075 | GEO

Discovery and functional interrogation of the virus and host RNA interactome of SARS-CoV-2 proteins [Ribo-Seq]

Project description:The coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Understanding the molecular functions of SARS-CoV-2 proteins is thus imperative to developing effective antiviral treatments. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs. SARS-CoV-2 proteins, NSP8 and NSP12, are found to specifically bind to untranslated regions of the RNA viral genome, with NSP12 additionally binding to all transcription regulatory sequences. This provides evidence for their central roles in replication and transcription. Moreover, we discovered a potential site of NSP12 mediated genome recombination, which could explain the genetic diversity found in coronaviruses. SARS-CoV-2 proteins exogenously expressed in human lung epithelial cells bind to 4,281 unique host RNAs. Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 which upregulates mitochondrial electron transport and N-linked glycosylation proteins. Furthermore, siRNA knockdown of NSP12-targeted proteins in human lung organoid cells demonstrates substantial antiviral effects. Conversely, NSP9 inhibits host gene expression via blocking mRNA export and dampens antiviral inflammation response such as interleukin 1α (IL1α) production. Our extensive viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics.

2022-03-31 | GSE198899 | GEO

Discovery and functional interrogation of the virus and host RNA interactome of SARS-CoV-2 proteins [eCLIP]

2022-03-09 | GSE173498 | GEO

Discovery and functional interrogation of the virus and host RNA interactome of SARS-CoV-2 proteins [RNA-Seq]

2022-03-09 | GSE173507 | GEO

SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition

Project description:Viruses hijack host cell metabolism to acquire the building blocks required for viral replication. Understanding how SARS-CoV-2 alters host cell metabolism could lead to potential treatments for COVID-19, the disease caused by SARS-CoV-2 infection. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface cultures and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces host cell oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes in host cell metabolism, we show that SARS-CoV-2 increases activity of mTORC1, a master regulator of anabolic metabolism, in cell lines and patient lung stem cell-derived airway epithelial cells. We also show evidence of mTORC1 activation in COVID-19 patient lung tissue. Notably, mTORC1 inhibitors reduce viral replication in kidney epithelial cells and patient-derived lung stem cell cultures. This suggests that targeting mTORC1 could be a useful antiviral strategy for SARS-CoV-2 and treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.

2021-02-19 | ST001709 | MetabolomicsWorkbench

The landscape of human brain immune response in patients with severe COVID-19

Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation and host immune response in acute COVID-19 cases. 3 brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering >99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed transcriptional changes in cortical microglia associated with a range of biological processes, including cellular activation, mobility and phagocytosis. Despite the absence of detectable SARS-CoV-2 in the brain at time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.

2021-06-16 | GSE164485 | GEO

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