Metagenomic sequencing of mpox virus clade Ib lesions
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB88042 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR14820706.fastq.gz | Fastqsanger.gz | |||
| ERR14820707.fastq.gz | Fastqsanger.gz | |||
| ERR14817849.fastq.gz | Fastqsanger.gz | |||
| ERR14817850.fastq.gz | Fastqsanger.gz |
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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 mpox outbreak of 2022–2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of T cell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics.
2023-09-29 | GSE234118 | GEO
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: Not available
| S-EPMC11646081 | biostudies-literature
Project description:Mpox, a zoonotic disease caused by the mpox virus (MPXV), has seen a significant shift in its epidemiological status since 2022, evolving from an initial local outbreak to a global epidemic. This recent outbreak of MPXV mainly emerged in several European and American countries and subsequently spread to over 100 countries and regions worldwide. The rapid evolution of MPXV, coupled with increased international interactions, has led to a gradual rise in mpox cases in certain regions of Asia, mostly involving MPXV clade II and its branch strains. In contrast, the more pathogenic and clinically severe MPXV clade Ib has been relatively rare, with no reports in China to date. Here, we analyzed the whole gene sequence of imported MPXV clade Ib variant from the first infection case detected in China. Through whole genome sequencing, we successfully obtained a full-length MPXV genome of 195,405 base pairs (bp). Phylogenetic analysis revealed that the genetic sequence of the MPXV in this case was predominantly clustered with MPXV clade Ib sequences previously reported from multiple African and European countries. Compared with the MPXV clade Ib reference strain DQ011155.1, there are 127 nucleotide alterations and 57 amino acid mutations in the MPXV genome of this case. Given that the MPXV clade Ib has started to appear in China, we must pay more attention to the prevention of and control measures for the spread of mpox.
| S-EPMC11768240 | biostudies-literature
Project description: Not available
| S-EPMC10914632 | biostudies-literature
Project description:Deep sequencing of mpox virus (MPOXV) from Madrid, Spain.
| PRJEB64429 | ENA