Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA574965 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10202965_1.fastq.gz | Fastqsanger.gz | |||
| SRR10202965_2.fastq.gz | Fastqsanger.gz | |||
| SRR10202966_1.fastq.gz | Fastqsanger.gz | |||
| SRR10202966_2.fastq.gz | Fastqsanger.gz | |||
| SRR10202967_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:A trimeric glycoprotein complex on the surface of human cytomegalovirus (CMV) binds to platelet-derived growth factor (PDGF) receptor α (PDGFRα) to mediate host cell recognition and fusion of the viral and cellular membranes. Soluble PDGFRα potently neutralizes CMV in tissue culture, and its potential use as an antiviral therapeutic has the benefit that any escape mutants will likely be attenuated. However, PDGFRα binds multiple PDGF ligands in the human body as part of developmental programs in embryogenesis and continuing through adulthood. Any therapies with soluble receptor therefore come with serious efficacy and safety concerns, especially for the treatment of congenital CMV. Soluble virus receptors that are orthogonal to human biology would reduce safety and efficacy concerns. This engineering problem is solved by deep mutational scanning on the D2-D3 domains of PDGFRα to identify variants that maintain interactions with the CMV glycoprotein trimer in the presence of competing PDGF ligands.
2020-06-01 | GSE138169 | GEO
Project description:A trimeric glycoprotein complex on the surface of human cytomegalovirus (HCMV) binds to platelet-derived growth factor (PDGF) receptor α (PDGFRα) to mediate host cell recognition and fusion of the viral and cellular membranes. Soluble PDGFRα potently neutralizes HCMV in tissue culture, and its potential use as an antiviral therapeutic has the benefit that any escape mutants will likely be attenuated. However, PDGFRα binds multiple PDGF ligands in the human body as part of developmental programs in embryogenesis and continuing through adulthood. Any therapies with soluble receptor therefore come with serious efficacy and safety concerns, especially for the treatment of congenital HCMV. Soluble virus receptors that are orthogonal to human biology might resolve these concerns. This engineering problem is solved by deep mutational scanning on the D2-D3 domains of PDGFRα to identify variants that maintain interactions with the HCMV glycoprotein trimer in the presence of competing PDGF ligands. Competition by PDGFs is conformation-dependent, whereas HCMV trimer binding is independent of proper D2-D3 conformation, and many mutations at the receptor-PDGF interface are suitable for functionally separating trimer from PDGF interactions. Purified soluble PDGFRα carrying a targeted mutation succeeded in displaying wild type affinity for HCMV trimer with a simultaneous loss of PDGF binding, and neutralizes trimer-only and trimer/pentamer-expressing HCMV strains infecting fibroblasts or epithelial cells. Overall, this work makes important progress in the realization of soluble HCMV receptors for clinical application.
| S-EPMC7329128 | biostudies-literature
Project description:Cytokines augment T cell function, but the nature of the optimal signals are not well defined. We deployed orthogonal cytokine-receptors to diversify the JAK/STAT signaling profiles elicited by orthogonal IL-2. We designed chimeric receptors consisting of the orthogonal IL-2 receptor extracellular domain (ECD) fused to intracellular domains (ICDs) from receptors for other common gamma chain cytokines as well as ICDs from interferon receptor, IL-10 receptor and homodimeric receptor families not expressed on T cells. Such non-natural pairings with the common gamma chain expand the JAK/STAT signaling space in T cells. Natural and non-natural orthogonal chimeric receptors led to distinct T cell fates in tumors, including naturally occurring states (Tc2 differentiation driven by orthogonal chimeric IL4R) and synthetic states (myeloid-like T cells driven by orthogonal chimeric granulocyte colony stimulating factor receptor). The orthogonal chimeric IL22R (o22R) potently activated STAT-1, -3, -4, and -5, imparting T cells with stem-like and effector properties. The pronounced anti-tumor functionality mediated by o22R and oGCSFR was linked to remodeling of the exhaustion-associated epigenome. Our study broadens the cytokine receptor repertoire, providing novel solutions to overcome barriers for using engineered T cells to treat cancer.
2024-07-29 | GSE272385 | GEO
Project description:Decoding murine cytomegalovirus
| PRJNA874807 | ENA
Project description:Murine Cytomegalovirus pSM3fr
| PRJEB64494 | ENA
Project description:Abstract: We have identified a cytomegalovirus virion protein capable of modulating the rapid induction of an interferon-like response in cells that follows virus binding and penetration. Functional genomics revealed a role for the major cytomegalovirus structural protein, pp65 (ppUL83), in counteracting this response. The underlying mechanism involves a differential impact of this structural protein on the regulation of interferon response factor 3 (IRF-3). In contrast, NF-{kappa}B is activated independent of pp65, and neither STAT1 nor STAT3 becomes activated by either virus. pp65 is sufficient to prevent the activation of IRF-3 when introduced alone into cells. pp65 acts by inhibiting nuclear accumulation of IRF-3 and is associated with a reduced IRF-3 phosphorylation state. Thus, this investigation shows that the major structural protein of cytomegalovirus is committed to the modulation of the IRF-3 response, a primary mediator of the type I interferon response. By subverting IRF-3, the virus escapes throwing a central alarm devoted to both immediate antiviral control and regulation of the immune response. Polyadenylated RNA from 107 confluent HFs was purified by using Oligotex (QIAGEN, Valencia, Calif.) from Trizol (Invitrogen)-extracted total RNA. This RNA was prepared, reverse transcribed, labeled with Cy3-dUTP or Cy5-dUTP (Amersham, Little Chalfont, Buckinghamshire, United Kingdom) by random primed synthesis with DNA pol I Klenow (Amersham Life Science, Inc., Cleveland, Ohio), and hybridized to spotted, human cDNA microarrays as previously described. Sequence-verified human cDNA microarrays (HE and HG series, 31,000 spots; HD51 series, 17,000 spots) were produced at Stanford. Images were collected by using a GenePix 4000B microarray scanner, manually flagged to eliminate poor spots and analyzed by GenePix Pro 2.0 (Axon, Union City, Calif.). A replicate experimental design type is where a series of replicates are performed to evaluate reproducibility or as a pilot study to determine the appropriate number of replicates for a subsequent experiments. User Defined
2006-01-18 | E-GEOD-4015 | biostudies-arrayexpress
Project description:Using Next-generation sequencing of total RNA isolated from human cytomegalovirus virions we have analyzed host (human) snoRNA molecules.
2021-03-05 | GSE168263 | GEO
Project description:Comparison of gene expression profiles of human foreskin fibroblasts (HFF) infected with 3 clinical isolates of cytomegalovirus strains representing three glycoprotein B genotypes. Keywords: other
2003-07-16 | GSE501 | GEO
Project description:Ring finger protein 41 (RNF41) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of many proteins such as ErbB3 receptors, BRUCE and parkin. Next to this, RNF41 regulates the intracellular trafficking of certain JAK-2 associated cytokine receptors by ubiquitinating and suppressing USP8 which in turn destabilizes the ESCRT-0 complex. To further elucidate the function of RNF41 we used different orthogonal approaches to reveal the RNF41 protein complex: Affinity Purification-Mass Spectrometry, BioID and Virotrap. We combined these results with known datasets for RNF41obtained with microarray MAPPIT and Y2H screens. By combining all these datasets , we provide a comprehensive high resolution interactome network. To further remove potential methodological artifacts from this network, we further distilled the data into a high confidence interactome map by retaining protein hits identified in two or more of the orthogonal methods. AP2S1, a novel RNF41 interaction partner, was selected from this high confidence interactome for further functional validation. We reveal a role for AP2S1 in leptin and LIF receptor signaling and show that RNF41 stabilizes and relocates AP2S1.
2018-03-26 | PXD007794 | Pride
Project description:Cytomegalovirus subverts macrophage identity
| PRJNA668749 | ENA