Ontology highlight
ABSTRACT:
PROVIDER: PRJNA869924 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21081565_1.fastq.gz | Fastqsanger.gz | |||
| SRR21081565_2.fastq.gz | Fastqsanger.gz | |||
| SRR21081566_1.fastq.gz | Fastqsanger.gz | |||
| SRR21081566_2.fastq.gz | Fastqsanger.gz | |||
| SRR21081567_1.fastq.gz | Fastqsanger.gz |
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Project description:The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.
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Project description:The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.
2023-02-13 | GSE225183 | GEO
Project description:The global spread of Monkeypox virus (MPXV) has resulted in the urgent need for an in-depth molecular characterization of the virus infection. Multiple omics studies on Vaccinia virus have extended our knowledge of poxvirus pathophysiology (REFs). Nevertheless, there are no comparative studies that would include an in-depth comparison of MPXV with other poxviruses in the context of molecular biology. Here, we report a comparative time-resolved proteomic study of MPXV and vaccinia viruses and a concurrent multi-omics study of MPXV infection in primary human cells. Using state-of-the-art proteomics, we profiled the virus-host interplay on the transcriptome, proteome and phosphoproteome levels in primary human foreskin fibroblasts. Pathway analysis in combination with projecting the gathered data onto the global network of host-signaling interactions revealed crosstalk between the perturbations at different levels, enabling identification of distinct and common molecular mechanisms of poxviruses. The NF-κB pathway, a signaling pathway governing immunomodulation and inflammation, was unexpectedly activated by MPXV but not VacV, while MPXV exhibited an astounding resistance to the effects of antiviral interferon response, potentially explaining the unique pathogenicity hallmarks of the monkeypox.
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Project description:The global spread of Monkeypox virus (MPXV) has resulted in the urgent need for an in-depth molecular characterization of the virus infection. Multiple omics studies on Vaccinia virus have extended our knowledge of poxvirus pathophysiology (REFs). Nevertheless, there are no comparative studies that would include an in-depth comparison of MPXV with other poxviruses in the context of molecular biology. Here, we report a comparative time-resolved proteomic study of MPXV and vaccinia viruses and a concurrent multi-omics study of MPXV infection in primary human cells. Using state-of-the-art proteomics, we profiled the virus-host interplay on the transcriptome, proteome and phosphoproteome levels in primary human foreskin fibroblasts. Pathway analysis in combination with projecting the gathered data onto the global network of host-signaling interactions revealed crosstalk between the perturbations at different levels, enabling identification of distinct and common molecular mechanisms of poxviruses. The NF-κB pathway, a signaling pathway governing immunomodulation and inflammation, was unexpectedly activated by MPXV but not VacV, while MPXV exhibited an astounding resistance to the effects of antiviral interferon response, potentially explaining the unique pathogenicity hallmarks of the monkeypox. Our extensive dataset highlights many signaling events and hotspots that influence the MPXV life cycle and may be used to guide rational design of both virus- and host-directed therapies, which we exemplify by identifying inhibitors of XXX, YYY, and ZZZ with potent antiviral efficacy against MPXV and/or VacV.
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Project description:Monkeypox virus (MPXV) is a double-stranded DNA virus that poses a significant threat to global public health security.In this project, we present data on the proteomics of F3L-transfected HEK293T cells, to identify the proteins interacting with MPXV-F3L protein by LC-MS,aiming to enhance our comprehension of F3L.
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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).
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