SARS-COV-2 N protein hijacks host NPM1-snoRNA to enhance rRNA 2’-O-Me modification and facilitate replication
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199130 | GEO | 2022/10/28
REPOSITORIES: GEO
Similar Datasets
Project description:SARS-CoV-2 coronavirus is one of the largest RNA viruses (26-32kb) and has emerged as a major threat to global public health. The resulting pandemic has caused global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype and a 382 deletion SARS-CoV-2 virus inside cells. We identified twelve potentially functional structural elements along the SARS-CoV-2 genome and observed that subgenomic viral RNA (sgRNAs) contains different structures that could be important for their functions using direct RNA sequencing. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host cellular RNAs. SARS-CoV-2 binds strongly to mitochondrial and nucleolar RNAs including COX1 and SNORD27, and contains 130 2’O-methylation sites along its genome. 2’O-methylation sites along the virus RNA are enriched in the UTRs and associated with increased pair-wise interactions. SARS-CoV-2 infection also results in a global decrease of 2’O-methylation sites on host mRNAs, suggesting that binding of SARS-CoV-2 to snoRNAs could be a pro-viral mechanism to sequester methylation machinery away from host RNAs to methylate the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, its cellular host factors and provides a platform for targeting the virus.
2021-07-05 | GSE165005 | GEO
Project description:SARS-COV-2 N protein hijacks host NPM1-snoRNA to enhance rRNA 2’-O-Me modification and facilitate replication
| PRJNA818624 | ENA
Project description:The ongoing COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people worldwide and has significant implications for public health. Host transcriptomics profiling provides comprehensive understanding of how the virus interacts with host cells and how the host responds to the virus. COVID-19 disease alters the host transcriptome, affecting cellular pathways and key molecular functions. To contribute to the global effort to understand the virus’s effect on host cell transcriptome, we have generated a dataset from nasopharyngeal swabs of 35 individuals infected with SARS-CoV-2 from the Campania region in Italy during the three outbreaks, with different clinical conditions. This dataset will help to elucidate the complex interactions among genes and can be useful in the development of effective therapeutic pathways
2023-05-25 | E-MTAB-13028 | biostudies-arrayexpress
Project description:SARS-CoV-2 pandemic has caused a dramatic health, social and economic crisis worldwide. To better understand the host-virus interactions and identify potentially targetable host factors, we have conducted CRISPR-Cas9 genetic screens using SARS-CoV-2 pseudotyped lentiviruses on human lung cancer cells. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: SPNS1 and PLAC8. Functional experiments with full SARS-CoV-2 viruses have confirmed that loss-of-function of these genes impairs viral entry. Importantly, we have found that PLAC8 is a key limiting host factor whose overexpression boosts viral infection in eight different human lung cancer cell lines. Using single-cell RNA-Seq data analyses, we demonstrate that PLAC8 is highly expressed in ciliated and secretory cells from the respiratory tract and in gut enterocytes, cell types that are highly susceptible to SARS-CoV-2 infection. Finally, proteomics and cell biology studies suggest that SPNS1 and PLAC8 affect viral entry through regulation of autophagy and lysosomal function.
2022-09-06 | PXD036334 | Pride
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: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
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
Project description:The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has led to an unparalleled global health crisis. While the majority of COVID-19 patients present with mild respiratory issues, a subset of patients still develop severe symptoms and life-threatening complications. Notably, abnormal coagulation and thrombosis are significant contributors to mortality in severe COVID-19 patients. Therefore, this study stimulated aortic endothelial cells with SARS-Cov-2 S protein and performed transcriptome sequencing analysis.
2024-12-15 | GSE283771 | GEO
Project description:SARS-CoV-2, a betacoronavirus with a positive-sense, single-stranded RNA genome, caused the COVID-19 pandemic with unprecedent health and socio-economic crisis. Although its general sense mRNA architecture was reported, that of its negative strand was unexplored. We combined poly(A)-mRNA and ribosomal RNA-depleted sequencing to delineate several fine features of both RNA strands. Together with the transcriptome data under the perturbation of anti-viral drug Remdesivir, this project opens new sights into SARS-CoV-2 replication mechanism and may facilitate the anti-viral drug design.
2021-06-27 | GSE160668 | GEO
Project description:SARS-CoV-2, the causative agent of the COVID-19 pandemic, drastically modifies infected cells in an effort to optimize virus replication. Included in this process is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammation and is a central driver of COVID-19 clinical presentations. Inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduces both cytokine production and viral replication. Here, we combined genetic screening with quantitative phosphoproteomics to better understand interactions between the p38/MAPK pathway and SARS-CoV-2. We found several components of the p38/MAPK pathway impact SARS-CoV-2 replication and that p38β is a critical host factor that promotes viral replication and prevents activation of the interferon pathway. Quantitative phosphoproteomics uncovered several SARS-CoV-2 nucleocapsid (N) protein phosphorylation sites near the N-terminus that were sensitive to p38 inhibition. Similar to p38β depletion, mutation of these N residues was associated with reduced viral replication and increased activation of Type I interferon signaling. Taken together, this study reveals a unique proviral function for p38β that is not shared with p38α, and supports efforts to develop p38β inhibitors as a strategy towards developing a new class of COVID-19 therapies. methods
2023-06-01 | PXD035451 | Pride