Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex [A549]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE198398 | GEO | 2022/12/13
REPOSITORIES: GEO
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Project description:This study reports a screen to identify putative inhibitors of the eIF4F complex for potential effects on blocking coronavirus replication, using HCoV-OC43 (OC43) infection of Vero E6 cells and the lung epithelial cancer line A549 as models.
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Project description:Transcriptional profiling of N-Tera2 differentiated human neuronal cells, comparing control uninfected cells to HCoV-OC43 infected cells at 24, 48 and 72 hour post-infection Keywords: Cell response to viral infection Two-condition experiment, N-Tera2 differentiated human neuronal cell mock infected vs. N-Tera2 differentiated human neuronal cell HCoV-OC43 infected at 24, 48 and 72 hours. Biological replicates: 2 at each time-course point. Technical replicate: 2 dye-swap at each time-point. 2 arrays hybridized with mock(cy3) vs infected(cy5) and 2 array with infected(cy3) vs mock(cy5).
2008-12-10 | E-GEOD-13879 | biostudies-arrayexpress
Project description:The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronavirus SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course transcriptomics, we confirmed that IGROV-1 cells exhibit a robust innate immune response upon SARS-CoV-2 infection, recapitulating the response previously observed in primary human nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens in IGROV-1 cells and identified Aryl hydrocarbon receptor (AHR) as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43. Using DiMNF, a small molecule inhibitor of AHR, we observed that the drug selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis in primary normal human bronchial epithelial cells revealed that DiMNF blocks HCoV-OC43 infection via basal activation of innate immune responses. Our findings highlight the potential of IGROV-1 cells as a valuable diagnostic and research tool to combat betacoronavirus diseases.
2023-09-19 | GSE237131 | GEO
Project description:The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of the common cold. Here, we generated a high-resolution atlas of the transcriptional and translational landscape of OC43 at various timepoints following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified several unannotated ORFs, including short upstream ORFs and a putative ORF nested inside the M gene. In parallel, we analyzed the cellular response to infection. Endoplasmic reticulum (ER) stress response genes are transcriptionally and translationally induced, but conventional antiviral genes remain mostly suppressed. At the same time, we observed widespread aberrant translation across cellular transcripts, including over 3′UTRs and of noncoding transcripts normally targeted by the nonsense mediated decay pathway. Taken together, our work provides a genomic resource for further study of OC43 and the cellular response to infection.
2024-01-17 | GSE252692 | GEO
Project description:We will use the EMC/2012 strain of the novel beta Coronavirus called Middle East Respiratory Syndrome Coronavirus (MERS-CoV). It was initially passaged on Vero E6 cells in Saudi Arabia before being sequenced at the Erasmus Medical College in Rotterdam, Netherlands by Dr Ron Fouchier. We propose to perform a time course of infection of hCoV-EMC on MRC5 cells (Human Lung origin) and Vero cells (African Green Monkey Kidney cells). Both cell lines readily grow and replicate the virus. Importantly these cell lines show signs of Cytopathic effect (CPE), such as cell rounding and release from the petri dish that coincide with time points high virus replication demonstrating the effects of virus replication on the cells. Transcriptomic analysis will be performed after infection with MERS-CoV and SARS-CoV (Urbani strain) to compare the host gene induction that occurs during infection. MRC5 and Vero E6 cells will be infected at an MOI of 0.1 and 3 and RNA harvested from cells at 24 and 48 post infection. RNA will be processed for library creation and sequenced on an Illumina Hiseq. Sequencing reads will be analyzed and compared across the time course and between each virus to identify common response pathways induced during infection as well as unique pathways specific to each virus.
2015-11-19 | E-GEOD-56193 | biostudies-arrayexpress
Project description:Transcriptional profiling of N-Tera2 differentiated human neuronal cells, comparing control uninfected cells to HCoV-OC43 infected cells at 24, 48 and 72 hour post-infection Keywords: Cell response to viral infection
2008-12-11 | GSE13879 | GEO
Project description:The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronavirus SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course transcriptomics, we confirmed that IGROV-1 cells exhibit a robust innate immune response upon SARS-CoV-2 infection, recapitulating the response previously observed in primary human nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens in IGROV-1 cells and identified Aryl hydrocarbon receptor (AHR) as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43. Using DiMNF, a small molecule inhibitor of AHR, we observed that the drug selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis in primary normal human bronchial epithelial cells revealed that DiMNF blocks HCoV-OC43 infection via basal activation of innate immune responses. Our findings highlight the potential of IGROV-1 cells as a valuable diagnostic and research tool to combat betacoronavirus diseases.
2023-09-19 | GSE237122 | GEO
Project description:Human coronavirus OC43 Raw sequence reads
| PRJNA313952 | ENA
Project description:We will use the EMC/2012 strain of the novel beta Coronavirus called Middle East Respiratory Syndrome Coronavirus (MERS-CoV). It was initially passaged on Vero E6 cells in Saudi Arabia before being sequenced at the Erasmus Medical College in Rotterdam, Netherlands by Dr Ron Fouchier. We propose to perform a time course of infection of hCoV-EMC on MRC5 cells (Human Lung origin) and Vero cells (African Green Monkey Kidney cells). Both cell lines readily grow and replicate the virus. Importantly these cell lines show signs of Cytopathic effect (CPE), such as cell rounding and release from the petri dish that coincide with time points high virus replication demonstrating the effects of virus replication on the cells. Transcriptomic analysis will be performed after infection with MERS-CoV and SARS-CoV (Urbani strain) to compare the host gene induction that occurs during infection.
2014-06-10 | GSE56192 | GEO
Project description:Viruses are obligate parasites that depend on the cellular machinery for their propagation. Several viruses also incorporate cellular proteins that facilitate viral spread. Defining these cellular proteins is critical to decipher viral life cycles and delineate novel therapeutic strategies. While numerous studies have explored the importance of host proteins in coronavirus spread, information about their presence in mature virions is limited. In this study, we developed a protocol to highly enrich mature HCoV-OC43 virions and characterize them by proteomics. Recognizing that cells release extracellular vesicles whose content is modulated by viruses, and given our ability to separate virions from these vesicles, we also analyzed their protein content in both uninfected and infected cells. We uncovered 69 unique cellular proteins associated with virions including 31 high confidence hits. These proteins primarily regulate RNA metabolism, enzymatic activities, vesicular transport, cell adhesion, metabolite interconversion and translation. We further discovered that the virus had a profound impact on exosome composition, incorporating 47 novel cellular proteins (11 high confidence) and excluding 92 others (61 high confidence) in virus-associated extracellular vesicles compared to uninfected cells. Moreover, a dsiRNA screen revealed that 11 of 18 select targets significantly impacted viral yields, including proteins found in virions or extracellular vesicles. Overall, this study provides new and important insights into the incorporation of numerous host proteins into HCoV-OC43 virions, their biological significance and the ability of the virus to modulate extracellular vesicles.
2024-06-24 | PXD052967 | Pride