Transcriptional Profiling of the Immune Response to Marburg Infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA251894 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever upon infection in humans and non-human primates. The mechanism of how this pathogenesis comes about is not well understood, but it is well accepted that pathogenesis is significantly driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of cynomolgus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptome of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The host response to aerosolized Marburg was evident at 1 day post-exposure. The response followed a 3-phase response that was led by a robust innate immune response. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus, and further suggested that the immune response may favor a Th2 response that would hamper the development of an effective antiviral immune response. Late infection events included the upregulation of coagulation associated factors. These findings suggest new avenues for investigating the pathogenesis of Marburg virus infection and provide rich dataset of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. RNA was isolated from a total of 30 PBMC samples from 15 cynomologus macaques infected with Marburg Virus. Samples were obtained at sequential timepoints post-infection, and included a pre-infection specimen from each animal. These samples were then processed and hybridized onto the Agilent 2-color arrays.
2015-05-11 | E-GEOD-58287 | biostudies-arrayexpress
Project description:Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever upon infection in humans and non-human primates. The mechanism of how this pathogenesis comes about is not well understood, but it is well accepted that pathogenesis is significantly driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of cynomolgus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptome of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The host response to aerosolized Marburg was evident at 1 day post-exposure. The response followed a 3-phase response that was led by a robust innate immune response. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus, and further suggested that the immune response may favor a Th2 response that would hamper the development of an effective antiviral immune response. Late infection events included the upregulation of coagulation associated factors. These findings suggest new avenues for investigating the pathogenesis of Marburg virus infection and provide rich dataset of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy.
2015-05-11 | GSE58287 | GEO
Project description:UnlabelledMarburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy.ImportanceMarburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the immune cells circulating in the blood of infected primates respond following exposure to Marburg virus. Our results show that there are three discernible stages of response to infection that correlate with presymptomatic, early, and late symptomatic stages of infection, a response format similar to that seen following challenge with other hemorrhagic fever viruses. In contrast to the ability of the virus to block innate immune signaling in vitro, the earliest and most sustained response is an interferon-like response. Our analysis also identifies a number of cytokines that are transcriptionally upregulated during late stages of infection and suggest that there is a Th2-skewed response to infection. When correlated with companion data describing the animal model from which our samples were collected, our results suggest that the innate immune response may contribute to overall pathogenesis.
| S-EPMC4577901 | biostudies-literature
Project description:Transcriptional Profiling of the Immune Response to Ebola Infection
| PRJNA283829 | ENA
Project description:Marburg virus, a member of the Filoviridae, is the causative agent of Marburg virus disease (MVD), a hemorrhagic fever with a case fatality rate of up to 90%. Acute kidney injury is common in MVD and is associated with increased mortality, but its pathogenesis in MVD remains poorly understood. Interestingly, autopsies show the presence of viral proteins in different parts of the nephron, particularly in proximal tubular cells (PTC). These findings suggest a potential role for the virus in the development of MVD-related kidney injury. To shed light on this effect, we infected primary human PTC with Lake Victoria Marburg virus and conducted transcriptomic analysis at multiple time points. Unexpectedly, infection did not induce marked cytopathic effects in primary tubular cells at 20 and 40 hours post infection. However, gene expression analysis revealed robust renal viral replication and dysregulation of genes essential for different cellular functions. The gene sets mainly downregulated in PTC were associated with the targets of the transcription factors MYC and E2F, DNA repair, the G2M checkpoint, as well as oxidative phosphorylation. Importantly, the downregulated factors comprise PGC-1α, a well-known factor in acute and chronic kidney injury. By contrast, the most highly upregulated gene sets were those related to the inflammatory response and cholesterol homeostasis. In conclusion, Marburg virus infects and replicates in human primary PTC and induces downregulation of processes known to be relevant for acute kidney injury as well as a strong inflammatory response.
2024-02-14 | GSE226148 | GEO
Project description:Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90%. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entire understood. In this study, we use microarrays to determine the host response to Ebola infection in the PBMCs of cynomolgus macaques.
2017-02-10 | GSE68809 | GEO
Project description:Infection of bats and cell cultures with Marburg, Ebola and Rabies viruses
| PRJNA640284 | ENA
Project description:The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria: Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC = Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis
2015-03-31 | E-GEOD-67427 | biostudies-arrayexpress
Project description:Methanothermobacter marburgensis str. Marburg genome sequencing project
| PRJNA40103 | ENA
Project description:Study was performed in order to determine the scope of antiviral response of Rousettus aegyptiacus-derived fibroblasts to Sendai and Marburg virus infection. This study aids in understanding the function of the expanded immune repertoire of Rosettus aegyptiacus.
2018-11-01 | GSE117367 | GEO