Ontology highlight
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PROVIDER: PRJNA1314986 | ENA |
REPOSITORIES: ENA
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Project description:Monkeypox virus (MPXV) infection-associated intestinal manifestations including diarrhea and proctitis have been frequently reported during mpox outbreaks. The clade IIb MPXV strain has caused the 2022-2023 global outbreak, whereas the Ia and Ib strains are causing the concurrent outbreaks in Africa. Here, we found clinical evidence that MPXV can directly infect human intestine to induce lesions. Intriguingly, primary organoids cultured from human ileum and rectum support productive infections of MPXV clade IIb, Ia and Ib strains. Upon differentiation, we found that enterocytes and goblet cells but not enteroendocrine cells are capable of supporting viral replication. Given that primary intestinal organoids can be rapidly expanded in large scale, we were able to screen a broad-spectrum antiviral drug library. We identified 12 leading candidates of safe-in-human agents including clinically used drugs such as clofarabine. We extensively validated the anti-MPXV activity of clofarabine in human intestinal and skin organoids, and consistently demonstrated the potent antiviral activity against clade Ia, Ib and IIb strains. These findings are important for better understanding the clinical manifestations of mpox. Primary intestinal organoids-based infection models and the established antiviral drug discovery pipeline bear major implications in responding to the current mpox global health emergency, and sustaining epidemic poxvirus preparedness.
2025-06-05 | GSE298715 | GEO
Project description:Mpox virus (MPXV) infection has different case fatality rates and symptoms depending on its clade. However, there has not been sufficient molecular biological analysis of the differences between clades. Here, we investigated whether we can distinguish between clades by focusing on the expression of MPXV genes. The replication efficiency of MPXV clade IIb, responsible for the 2022 Mpox outbreak, was lower than that of clades Ia and IIa. We found that OPG175 was highly expressed in MPXV clade IIb-infected cells. Suppression of OPG175 expression significantly upregulated the infectious titer of MPXV, while OPG175 overexpression significantly decreased the infectious titer of MPXV. We found OPG175 overexpression to enhance the expression of Wnt signaling-related genes and activation of Wnt signaling to decrease the replication efficiency of MPXV. Therefore, high OPG175 expression in MPXV clade IIb-infected cells likely inhibits MPXV replication via activation of Wnt signaling.
2025-10-24 | GSE278866 | GEO
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.
2023-06-06 | GSE219036 | GEO
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:Orthopoxviruses are large DNA viruses which can cause disease in numerous host species. Even though the eradication of variola virus - the causative agent of human smallpox M-bM-^@M-^S succeeded, with the end of vaccinations several other orthopoxviruses emerged as potential threat to human health. For instance, animal-borne monkeypox virus, cowpox virus and closely related vaccinia virus are all capable of establishing zoonotic infections in humans. The disease caused by each virus differs in terms of expression and severity, but we still know little about the reasons for these different phenotypes. They may be explained by the unique repertoire of host cell modulating factors encoded by each virus. In this study, we aimed at characterizing the specific modulation of the host cells gene expression profile by orthopoxvirus infection. In our study we analyzed changes in host cell gene expression of HeLa cells after infection with cowpox virus, monkeypox virus or vaccinia virus and compared these to each other and to the gene expression profile of non-infected cells using Agilent Whole Genome Microarray technology. We could identify major differences in viral modulation of host cell immune response genes, especially an induction of genes involved in leukocyte migration and Toll-like receptor signalling in cowpox and monkeypox virus infected cells. This was not observed following vaccinia virus infection. If these differences contribute to the different clinical manifestation of cowpox, monkeypox and vaccinia virus infections in certain host species remains to be elucidated. We analyzed the gene expression profile of HeLa cells wich were either mock-infected or infected with Vaccinia virus strain IHD-W, Cowpox virus strain Brighton Red or Monkeypox virus strain MSF#6 at a multiplicity of infection of 5. Experiments were performed in duplicate. At 6 h post infection total RNA was isolated from infected cells and used for microarray analysis.
2012-04-14 | E-GEOD-36854 | biostudies-arrayexpress
Project description:Patients with mpox may present with a skin rash and mild respiratory symptoms, including sore throat and cough. The genome of the mpox virus (MPXV) has been detected in throat swab specimens from some mpox patients, indicating potential involvement of the respiratory tract. In this study, we used lung organoids to investigate the effects of MPXV infection on the respiratory system by evaluating the viral replication and the infection-mediated host response. MPXV infection resulted in the accumulation of high levels of viral genomes within the cells. H&E staining showed almost no histological differences between MPXV-infected lung organoids and uninfected lung organoids. In addition, RNA-seq analysis revealed that MPXV infection did not significantly alter the gene expression levels of various lung markers. MPXV infection did not change the production of proinflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-beta (IFN-β). These findings suggest that MPXV can replicate in lung organoids without significantly affecting their cellular function.
2025-11-01 | GSE287262 | GEO
Project description:Orthopox viruses, including monkeypox, multiply intracellularly and induce numerous changes in host genes expression. The virus target mainly humoral host response, and simultaneously, exploits other genes and functions to reproduce effectively. The goal of this experiment is to identify those host genes and functions that are essential for monkeypox virus replication. Mock infected control cells were treated and incubated identically to time point arms, except for virus exposure. Two time points of cells infected with monkeypox virus were harvested at 3, 7 hours post infection, and gene expression was assessed using microarray in all arms. The experiment was done in triplicate.
2010-04-07 | E-GEOD-21001 | biostudies-arrayexpress
Project description:Orthopoxviruses are large DNA viruses which can cause disease in numerous host species. Even though the eradication of variola virus - the causative agent of human smallpox – succeeded, with the end of vaccinations several other orthopoxviruses emerged as potential threat to human health. For instance, animal-borne monkeypox virus, cowpox virus and closely related vaccinia virus are all capable of establishing zoonotic infections in humans. The disease caused by each virus differs in terms of expression and severity, but we still know little about the reasons for these different phenotypes. They may be explained by the unique repertoire of host cell modulating factors encoded by each virus. In this study, we aimed at characterizing the specific modulation of the host cells gene expression profile by orthopoxvirus infection. In our study we analyzed changes in host cell gene expression of HeLa cells after infection with cowpox virus, monkeypox virus or vaccinia virus and compared these to each other and to the gene expression profile of non-infected cells using Agilent Whole Genome Microarray technology. We could identify major differences in viral modulation of host cell immune response genes, especially an induction of genes involved in leukocyte migration and Toll-like receptor signalling in cowpox and monkeypox virus infected cells. This was not observed following vaccinia virus infection. If these differences contribute to the different clinical manifestation of cowpox, monkeypox and vaccinia virus infections in certain host species remains to be elucidated.
2012-04-15 | GSE36854 | GEO
Project description:Metagenomic sequencing of mpox virus clade Ib lesions
| PRJEB88042 | ENA