HCMV benchmarking
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB32127 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3276890_1.fastq.gz | Fastqsanger.gz | |||
| ERR3276890_2.fastq.gz | Fastqsanger.gz | |||
| ERR3276891_1.fastq.gz | Fastqsanger.gz | |||
| ERR3276891_2.fastq.gz | Fastqsanger.gz | |||
| ERR3276892_1.fastq.gz | Fastqsanger.gz |
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Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as 'vehicles' for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-kB activity. Integrins, which are upstream of the PI(3)K and NF-kB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination. Monocytes were mock-infected, HCMV-infected, or pretreated with PP2 inhibitor prior to HCMV infection. There were three samples analyzed per individual replicate. Three replicates are included. comparative studies with a use of the specific Src kinase activity inhibitor
2010-10-31 | E-GEOD-24238 | biostudies-arrayexpress
Project description:Data-independent acquisition assessment of human fibroblasts and epithelial cells infected with different strains of human cytomegalovirus (HCMV). Viruses are ubiquitous entities that infect organisms across the kingdoms of life. While viruses can infect a range of cells, tissues, and organisms, this aspect is often not explored in cell culture analyses. There is limited information about which infection-induced changes are shared or distinct in different cellular environments. The prevalent pathogen HCMV remodels the structure and function of subcellular organelles and their interconnected networks formed by membrane contact sites (MCSs). A large portion of this knowledge has been derived from fibroblasts infected with a lab-adapted HCMV strain. Here, we assess strain- and cell type-specific alterations in MCSs and organelle remodeling induced by HCMV. Integrating quantitative mass spectrometry, super-resolution microscopy, and molecular virology assays, we compare infections with lab-adapted and low-passage HCMV strains in fibroblast and epithelial cells. We determine that, despite baseline proteome disparities between uninfected fibroblast and epithelial cells, infection induces convergent changes and is remarkably similar. We show that hallmarks of HCMV infection in fibroblasts, mitochondria-ER encapsulations (MENCs) and peroxisome proliferation, are also conserved in infected epithelial and macrophage-like cells. Exploring cell type-specific differences, we demonstrate that fibroblasts rely on endosomal cholesterol transport while epithelial cells rely on cholesterol from the Golgi. Despite these mechanistic differences, infections in both cell types result in phenotypically similar cholesterol accumulation at the viral assembly complex. Our findings highlight the adaptability of HCMV, in that infections can be tailored to the initial cell state by inducing both shared and unique proteome alterations, ultimately promoting a unified pro-viral environment.
2024-06-20 | MSV000095094 | MassIVE
Project description:In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identification of the repertoire of T-cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. We applied a novel approach which employs HCMV deletion mutant viruses, lacking HLA class I immunoevasins. Infection of human fibroblast cell lines with those mutant viruses allowed the direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. Using this strategy, we identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T-cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. The unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T-cell specificities in seropositive individuals. This approach proved to be superior to procedures applying in silico analysis to identify true viral antigens.
2019-11-20 | PXD013120 | Pride
Project description:Primary infection with Human cytomegalovirus (HCMV) results in a persistent lifelong infection due to its ability to establish latent infection. During productive HCMV infection, viral genes are expressed in a coordinated cascade that is characteristic of all herpesviruses and traditionally relies on the dependencies of viral genes on protein synthesis and viral DNA replication. In contrast, the transcriptional landscape associated with HCMV latency is still disputed and poorly understood. Here, we examine viral transcriptomic dynamics during the establishment of both productive and latent HCMV infections. These temporal measurements reveal that viral gene expression dynamics along productive infection and their dependencies on protein synthesis and viral DNA replication, do not fully align. This illustrates that the regulation of herpesvirus genes does not represent a simple sequential transcriptional cascade and surprisingly many viral genes are regulated by multiple independent modules. Using our improved classification of viral gene expression kinetics in conjunction with transcriptome-wide measurements of the effects of a wide array of chromatin modifiers, we unbiasedly show that a defining characteristic of latent cells is the unique repression of immediate early (IE) genes. In particular, we demonstrate that IE1 (a central IE protein) expression is the principal barrier for achieving a full productive cycle. Altogether, our findings provide an unbiased and elaborate definition of HCMV gene expression in lytic and latent infection states.
2022-03-29 | GSE193467 | GEO
Project description:HCMV latnecy within hematopoetic precursor cells was evaluated by infecting cells and establishing latency using a recombinant virus that allows for labeing of RNA species only in the context of a viral infection thereby allowing purification of these transcripts from mock infected cells. We used microarrays to detail the global programme of gene expression to identify changes in host transcription during HCMV latency.
2018-04-24 | GSE113551 | GEO
Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as “vehicles” for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-κB activity. Integrins, which are upstream of the PI(3)K and NF-κB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination.
2010-10-31 | GSE24238 | GEO
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217710 | GEO
Project description:Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-16 | GSE217713 | GEO
Project description:Infection with Human cytomegalovirus (HCMV) can result in either productive or non-productive infection, the latter potentially leading to establishment of latency, but the molecular factors that dictate these different infection outcomes are elusive. Macrophages are known targets of HCMV and considered to be permissive for productive infection, while monocytes, their precursors, are thought to support latent infection. Here we reveal that infection of macrophages is more complex than previously appreciated and can result in either productive or non-productive infection. By analyzing the progression of HCMV infection in c and macrophages using single cell transcriptomics, we uncover that the key characteristics that define productive and non-productive cells are the onset of viral gene expression, and activation of Interferon-stimulated genes (ISGs), respectively. We show that the level of viral gene expression, and specifically the expression of the major immediate early factor, IE1, is the principle barrier for establishing productive infection. On the cellular side, induction of ISGs in response to infection surprisingly does not dictate infection outcome, but we find that the cell intrinsic ISG levels is a main determinant of infection outcome. Indeed, intrinsic ISG level is downregulated with monocyte differentiation. We further show that, compared to monocytes, non-productive macrophages maintain slightly higher levels of viral transcripts and are able to reactivate, raising the possibility that they can serve as latency reservoirs in tissues. Moreover, we find that productive infection perturbs macrophage identity and function, likely affecting their immunological role during active infection. Overall, by harnessing the tractable system of monocyte differentiation we decipher the underlying principles that control HCMV infection outcome, and propose macrophages as a new potential HCMV reservoir in tissues.
2023-01-05 | GSE189581 | GEO
Project description:Purpose: to compare viral gene expression in HCMV infected Kasumi-3 cells at 4 and 24 hours post infection
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