Diversity in the polyadenylation and decay of human cellular microRNAs during Vaccinia virus infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54235 | GEO | 2015/07/15
SECONDARY ACCESSION(S): PRJNA236014
REPOSITORIES: GEO
Similar Datasets
Project description:Vaccinia virus (VACV) is a large cytoplasmic dsDNA virus that causes dramatic alterations to many cellular pathways including microRNA biogenesis. Here we use small RNA sequencing to comprehensively quantify the impact of VACV infection on the expression of endogenous small non-coding RNAs (sncRNAs) at both early (6 h) and late (24 h) times post infection. Non-coding RNAs (sncRNAs) were assessed at 6 hours and 24 hours, in naive and VACV-infected HeLa cells, in the presence or absence of the inhibitor AraC. There were three replicates for each of the eight groups.
2015-07-15 | E-GEOD-54235 | biostudies-arrayexpress
Project description:Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of IRF-3, NF-κB and type I interferon (IFN) signaling. Here, we used highly multiplexed proteomics to quantify >8,000 cellular proteins and ~80% of viral proteins over seven time points spanning the whole course of VACV infection. This identified multiple novel viral targets, including putative natural killer cell ligands and IFN-stimulated genes. The class II histone deacetylase HDAC5 was selectively degraded early during VACV infection. Use of cell lines in which HDAC5 was overexpressed or knocked out showed that HDAC5 restricted replication of both VACV and herpes simplex virus type 1 (HSV-1). By generating a protein-based temporal classification of VACV gene expression, we identified the early protein C6, a multifunctional IFN antagonist, as the factor that targets HDAC5 for proteasomal degradation. Our approach thus identifies both a novel restriction factor and a viral mechanism of innate immune evasion.
2019-05-07 | PXD012785 | Pride
Project description:Primary human astrocytes were infected with either monkeypox virus (MPXV clade IIb lineage), vaccinia virus (VACV: Acambis 2000), or controls (MC=monkeypox control, AC = Vaccinia control) at an MOI of 10 for 6 h. Samples (n=4) were analyzed by LC-MS/MS with label-free quantification where the data was acquired by data-dependent acquisition (DDA).
2023-06-21 | MSV000092229 | MassIVE
Project description:Vaccinia virus (VACV) encodes decapping enzyme D10 that suppresses gene expression by removing the protective 5’ cap off mRNAs, rendering them susceptible to degradation by cellular exonucleases. Here, we use RNA-seq to profile the repertoire of transcripts targeted by D10 in isolation as well as in the context of VACV infection. We found that D10 is a broadly acting decapping enzyme and targets the vast majority of human transcripts. Notably, we found that the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, with transcripts derived from intronless genes being less susceptible to D10 activity. Since all viral genes are intronless, and some viral transcripts are uncapped, D10 preferentially targets host transcripts over viral transcripts. The disproportionate activity of D10 towards host transcripts may help the virus restrict host innate immune response and shift the translational resources towards viral protein synthesis.
2022-02-02 | GSE185520 | GEO
Project description:Modified vaccinia Ankara (MVA) immunisation is being deployed to curb the current outbreak of mpox in multiple countries1. Originally authorized for vaccination against smallpox, MVA is a vaccinia virus (VACV) strain that does not replicate in human cells or cause serious adverse events. Here, we conducted a highly multiplexed proteomic analysis2 to quantify >9,000 cellular proteins and ~80% of viral proteins at five time points throughout MVA infection of human cells3. 690 human proteins were down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets, including multiple components of the nuclear pore complex (NPC), were not shared with VACV-Western Reserve4, which is derived from a first generation smallpox vaccine associated with serious adverse events. Using pharmacological inhibition of viral DNA replication and heat-inactivated virions, we discovered that post-replicative gene expression is necessary for the downregulation of NPC proteins and for elements of MVA antagonism of innate immune sensing. Our approach thus provides the first global view of the impact of MVA infection on the host proteome, offers insights into how MVA interacts with the antiviral defences and identifies cellular mechanisms that may underpin the abortive infection of human cells. These discoveries will prove vital to the rational design of future generations of vaccines.
2023-10-11 | PXD039034 | Pride
Project description:Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. This therapy relies on efficient replication of virus in tumor cells in vivo with minimal or no replication in normal tissues. We recently described GLV-1h68 as a modified Vaccinia Virus (VACV) construct with exclusive in vivo tropism for tumor cells in experimental animal models. Moreover, we had previously observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro during the first 20 hours following infection and the in vivo ability to colonize and eliminate the corresponding tumor implant. Thus, we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines, extensively characterized and used for the assessment of novel therapeutic modalities. All cell lines were cultured and infected in identical conditions. Pre-infection transcriptional profiling was obtained to search for correlates of permissivity to viral infection. Selected cell lines were also tested for permissivity to another VACV and a vesicular stomatitis virus (VSV) strain. We observed that permissivity to VACV infection during the first 20 hours is quite heterogeneous among cell lines but highly reproducible within each cell line. The tissue of origin of each cell line does not influence permissivity to infection with the exception of B cell derivation. Permissivity correlates between two VACV constructs and between them and VSV suggesting a common permissive phenotype. No clear transcriptional pattern predictive of permissivity to infection could be identified though weak associations were observed that suggest a multifactorial control of viral replication. This study adds to the current characterization of the NCI-60 panel to guide the design and interpretation of experimental models testing oncolytic therapies.
2012-03-24 | GSE28472 | GEO
Project description:The interaction between immune cells and virus-infected targets involves multiple plasma membrane (PM) proteins. A systematic study of PM protein modulation by vaccinia virus (VACV), the paradigm of host regulation, has the potential to reveal not only novel viral immune evasion mechanisms, but also novel factors critical in host immunity. Here, >1000 PM proteins were quantified throughout VACV infection, revealing selective downregulation of known T and NK cell ligands including HLA-C, downregulation of cytokine receptors including IFNAR2, IL-6ST and IL-10RB, and rapid inhibition of expression of certain protocadherins and ephrins, candidate activating immune ligands. Downregulation of most PM proteins occurred via a proteasome-independent mechanism. Upregulated proteins included a decoy receptor for TRAIL. Twenty VACV-encoded PM proteins were identified, of which five were not recognised previously as such. Collectively, this dataset constitutes a valuable resource for future studies on antiviral immunity, host-pathogen interaction, poxvirus biology, vector-based vaccine design and oncolytic therapy.
2022-06-01 | PXD033407 | Pride
Project description:Viral infection both activates stress signaling pathways and redistributes ribosomes away from host mRNAs to translate viral mRNAs. The intricacies of this ribosome shuffle from host to viral mRNAs are poorly understood Here, we uncover a role for the ribosome associated quality control (RQC) factor, ZNF598, during vaccinia virus mRNA translation. ZNF598 acts on collided ribosomes to ubiquitylate 40S subunit proteins uS10 and eS10 initiating RQC-dependent nascent chain degradation and ribosome recycling We show that vaccinia infection in human cells enhances uS10 ubiquitylation indicating an increased burden on RQC pathways during viral propagation. Consistent with an increased RQC demand, we demonstrate that vaccinia virus replication is impaired in cells which either lack ZNF598 or express a ubiquitylation deficient version of uS10 Using SILAC-based proteomics and concurrent RNAseq analysis, we determine that translation and not transcription of vaccinia virus mRNAs is compromised in cells with deficient RQC activity. Additionally, vaccinia virus infection reduces cellular RQC activity, suggesting that co-option of ZNF598 by vaccinia virus plays a critical role in translational reprogramming that is needed for optimal viral propagation.
2021-04-14 | GSE165732 | GEO
Project description:Cowpox virus (CPXV) causes most zoonotic orthopoxvirus (OPV) infections in Europe and Northern as well as Central Asia. The virus has the broadest host range of OPV and is transmitted to humans from rodents and other wild or domestic animals. Increasing numbers of human CPXV infections in a population with declining immunity have raised concerns about the virus’ zoonotic potential. While there have been reports on the proteome of other human-pathogenic OPV, namely vaccinia virus (VACV) and monkeypox virus (MPXV), the protein composition of the CPXV mature virion (MV) is unknown. This study focused on the comparative analysis of the VACV and CPXV MV proteome by label-free single-run proteomics using nano liquid chromatography and high-resolution tandem mass spectrometry (nLC-MS/MS).
2015-11-16 | PXD003013 | Pride
Project description:Viral diseases have alwanys been intricate and persistent issues throughout the world and lack of holistic discoveries of molecular dysregulations of virus-host interactions. The temporal proteomics strategy can identify various differentially expressed proteins and offer collaborated interaction networks under pathological conditions. Herein, temporal proteomics at various hours post infection of Vero cells were launched to uncover molecular alternations during vaccinia virus-induced cell migration. Different stages of infection were included to differentiate gene ontologies and critical pathways at specific time points of infection. The enrichment of functional interaction networks and pathways verified the significances of regulation of actin cytoskeleton and lamellipodia during vaccinia virus-induced fast cell motility. Current results offer the systematic proteomic profiling og molecular dysregulations at different stages of vaccinia virus infection and potential biomedical targets for treating viral diseases.
2023-05-04 | PXD040845 | Pride