Project description:The Monkeypox virus (MPXV) is a neurotropic zoonotic pathogen, as evidenced by neurological symptoms in patients and its demonstrated neuroinvasive potential in both in vitro and in vivo models. However, the host responses and mechanisms underlying MPXV-induced neural damage remain poorly understood. To address this gap, we performed transcriptomic profiling and functional validation across three human neuronal cell lines (U87MG, SH-SY5Y, and HMC3) to investigate MPXV-induced molecular alterations. Among these cell types, U87MG cells exhibited the most pronounced transcriptional changes. Specifically, MPXV infection activated the MAPK signaling pathway (ERK1/2 and p38) and elicited a strong pro-inflammatory response, characterized by elevated TNF-α, IL-16, IL-17, and IL-1β. In parallel, immune evasion signatures were detected, including upregulation of MOGS, DICER1, and VPS13A, along with downregulation of STAT1 and IFIT family genes. Notably, MPXV markedly suppressed ADAR1, a key RNA-editing enzyme essential for neural homeostasis and antiviral defense, thereby implicating ADAR1 dysregulation as a driver of virus-induced neuroinflammation and injury.
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 A23R-transfected HEK293T cells, to identify the proteins interacting with MPXV-A23R protein by LC-MS,aiming to enhance our comprehension of A23R.
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.
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.
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.
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.
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.
Project description:Background: The global emergence of monkeypox virus (MPXV) highlights the urgent need for a deeper understanding of host–pathogen interactions. Although transcriptional responses to MPXV infection have been characterized, the role of epitranscriptomic regulation particularly N6‑methyladenosine (m6A) modification remains largely unexplored. Methods: We performed an integrated analysis of time‑series transcriptomic and m6A methylome profiles using whole blood samples collected from MPXV‑infected rhesus macaques at 7, 14, and 21 days post‑infection, with distinct animals used at each time point. Host gene expression and m6A modification dynamics were examined over the course of infection. Differential expression and differential m6A modification analyses were conducted, followed by integrative pathway and immune cell signature profiling. Results: MPXV infection induced sustained host reprogramming, characterized by suppression of immune pathways and activation of metabolic processes. A global increase in m6A modifications was observed, accompanied by upregulation of the methyltransferase METTL3 and downregulation of demethylases (FTO, ALKBH5) and readers (YTHDF1-3). Knockdown of METTL3 or YTHDF2 reduced viral replication, suggesting a proviral role for this regulatory circuit. Integrative analysis identified 38 genes with coordinated changes in both transcription and m6A modification across all three time points. Focusing on literature-curated pathogenic pathways, we further identified 11 dual-regulated host factors. Notably, DNAJB1 was the only gene shared between these two independent selection strategies. m6A peaks near transcription start sites and within 5′UTR positively correlated with gene expression, whereas coding region modifications showed weak negative correlations. Immune lineage signatures showed gradual declines in T cell, NK, and monocyte/macrophage signatures with a progressive increase in B cell signatures. Cross‑dataset comparison confirmed core m6A regulatory trends despite heterogeneity across tissues and viral strains. Conclusions: This study reveals m6A epitranscriptomic remodeling as a key correlate of the host response to MPXV infection and nominates DNAJB1 alongside the other 10 dual‑regulated genes as candidate host factors for further mechanistic investigation.
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).