Herpesvirus remodel organization and function of mitochondria as infection proceeds
Ontology highlight
ABSTRACT:
ORGANISM(S): Chlorocebus aethiops
PROVIDER: GSE243613 | GEO | 2024/03/18
REPOSITORIES: GEO
Similar Datasets
Project description:We profile the peripheral blood of patients infected with West Nile Virus with divergent disease-trajectories (West Nile Encephalitis, West Nile Fever, and asymptomatic) during relatively acute infection and at a convalescent timepoint (~90-days later) using single-cell RNA sequencing in an effort to uncover determinants of disease progression and flesh out the landscape of infection. In the blood of the infected patients, stratified cell-states involved in acute viral infection resolve into more homogenous states at the follow-up blood draws, A dramatic shared transcriptional shift between the primary blood-draws during acute infection and the 90-day follow-ups in all observed compartments allows us to highlight multiple cell-type and cell-state-specific patterns of gene expression.
2021-12-24 | GSE142595 | GEO
Project description:DNA copy number variations occur within populations and aberrations can cause disease. We sought to develop an improved lab-automatable, cost-efficient, accurate platform to profile DNA copy number. We developed a sequencing-based assay of nuclear, mitochondrial, and telomeric DNA copy number that draws on the unbiased nature of next-generation sequencing and incorporates techniques developed for RNA expression profiling. To demonstrate this platform, we assayed UMC-11 cells using 5 million 33 nt reads and found tremendous copy number variation, including regions of single and homogeneous deletions and amplifications to 29 copies; 5 times more mitochondria and 4 times less telomeric sequence than a pool of non-diseased, blood-derived DNA; and that UMC-11 was derived from a male individual. The described assay outputs absolute copy number, outputs an error estimate (p-value), and is more accurate than array-based platforms at high copy number. The platform enables profiling of mitochondrial levels and telomeric length. The assay is lab-automatable and has a genomic resolution and cost that are tunable based on the number of sequence reads. DNA genome sequencing at roughly 0.03 coverage to identify genomic copy number variations
2010-04-02 | E-GEOD-21159 | biostudies-arrayexpress
Project description:Despite the essential role of the outer mitochondrial membrane (OMM) in cellular homeostasis, little is known of the mechanisms that remodel it during naturally occurring stresses. Here, we report a previously undescribed structure we term SPOT (structure positive for outer mitochondrial membrane) that is up to 10 m in diameter and emerges from the OMM during infection with the human parasite Toxoplasma gondii. SPOTs are distinct from mitochondria-derived vesicles and compartments, and mediate the depletion of the OMM proteins MFN1 and MFN2 that restrict parasite growth. The formation of SPOTs depends on the parasite effector protein TgMAF1 and the host mitochondrial import receptor TOM70, which is required for optimal parasite proliferation. TOM70 enables TgMAF1 to interact with host SAM50, a major translocase of the OMM, and SAM50 inhibition or acute mitochondrial import stress are sufficient to promote SPOT formation independently of infection. We propose that Toxoplasma exploits SPOTs, a cellular response to OMM import stress, to promote its growth.
2022-08-04 | PXD024491 | Pride
Project description:Mammals are co-infected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine gammaherpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-g (IFNg) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNg reactivated latent murine gammaherpesvirus infection in vivo, suggesting a âtwo-signalâ model for viral reactivation. Thus chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status. All of the RNA from virus-pos cells and 50 ng of RNA from virus-neg cells was prepared for RNA-seq using ScriptSeq v2 RNA-seq library preparation kit (Epicentre). Index Primers (Epicentre) were added and samples underwent Duplex-Specific thermostable nuclease (DSN) (Evrogen) treatment to remove ribosomal RNA. Samples were pooled and sequenced on HiSeq.
2014-06-26 | E-GEOD-58116 | biostudies-arrayexpress
Project description:Mammals are co-infected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine gammaherpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-g (IFNg) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNg reactivated latent murine gammaherpesvirus infection in vivo, suggesting a ‘two-signal’ model for viral reactivation. Thus chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status.
2014-06-26 | GSE58116 | GEO
Project description:Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions
| PRJNA687728 | ENA
Project description:DNA copy number variations occur within populations and aberrations can cause disease. We sought to develop an improved lab-automatable, cost-efficient, accurate platform to profile DNA copy number. We developed a sequencing-based assay of nuclear, mitochondrial, and telomeric DNA copy number that draws on the unbiased nature of next-generation sequencing and incorporates techniques developed for RNA expression profiling. To demonstrate this platform, we assayed UMC-11 cells using 5 million 33 nt reads and found tremendous copy number variation, including regions of single and homogeneous deletions and amplifications to 29 copies; 5 times more mitochondria and 4 times less telomeric sequence than a pool of non-diseased, blood-derived DNA; and that UMC-11 was derived from a male individual. The described assay outputs absolute copy number, outputs an error estimate (p-value), and is more accurate than array-based platforms at high copy number. The platform enables profiling of mitochondrial levels and telomeric length. The assay is lab-automatable and has a genomic resolution and cost that are tunable based on the number of sequence reads.
2010-04-02 | GSE21159 | GEO
Project description:This ordinary differential equation model is described in the following article:
"Autocrine and paracrine interferon signalling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host"
G. Michael Lavigne, Hayley Russell, Barbara Sherry and Ruian Ke
DOI: 10.1098/rspb.2020.3002
Comment:
This model is based on the ordinary differential equations of the non-spatial model of well-mixed viral infection stated in the manuscript (Eq. 2.1 in the article).
Abstract:
The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.
2021-08-11 | BIOMD0000001021 | BioModels
Project description:We report here that human mitochondria contain small RNA including microRNA, piRNA, tRNA, rRNA, and RNA repeats. Mitochondria from human cells were purified and RNA isolated. Small RNAs were purified, library generated and analyzed by Illumina Hiseq 2000 system. The sequencing generated 19.5 and 17.7 million reads from HEK-293 and HeLa respectively. 91% and 97% sequences of HEK293 and HeLa respectively were annotated to various classes of small RNA. The total percentage of 4.21 and 2.58 sequences from HEK293 and HeLa respectively was found to be of miRNA. Further, we found only 1.2 % sequences from both the libraries aligned to mitochondrial genome. These results suggest that there is efficient transport of nuclear encoded small RNA to mitochondria. The small RNA in mitochondria may regulate critical cellular processes. Analyzing the smallRNA in human mitochondria from two human cell lines (HEK-293 and HeLa).
2013-03-05 | E-GEOD-32185 | biostudies-arrayexpress
Project description:Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi’s sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). We have previously described evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH). We speculated that viral infection of the pulmonary microvascular endothelial cells could cause the angioproliferative phenotype characteristic of severe pulmonary arterial hypertension (PAH). We now demonstrate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells (HPMVECs) in vitro, confirming both latent and lytic infection. HHV-8 infection of HPMVECs resulted in significant changes of gene expression including alterations of pathways integral to both cellular apoptosis and angiogenesis. This infection also results in alterations of genes integral to the bone morphogenic protein (BMP) pathway, including down regulation of bone morphogenic protein receptor 1a (BMPR1a) and bone morphogenic protein 4 (BMP4). Other genes previously implicated in the development of PAH are also altered in expression by HHV-8 infection. These include increased expression of Interleukin-6 (IL-6) and the matrix metalloproteinases (MMP)-1, MMP-2 and MMP-10. Lastly, cells infected with HHV-8 apoptosis resistant. Infection of pulmonary microvascular endothelial cells with human herepesvirus-8 results in alteration of the BMP pathway as well as an anti-apoptotic phenotype, consistent with the development of plexiform lesions characteristic of pulmonary arterial hypertension. Keywords: Viral infection of endothelial cells in culture
2008-04-30 | GSE6489 | GEO