{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137044393144192.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0914843107"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0914843107"}}],"dc:title":[{"@value":"Functional delivery of viral miRNAs via exosomes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n                    Noncoding regulatory microRNAs (miRNAs) of cellular and viral origin control gene expression by repressing the translation of mRNAs into protein. Interestingly, miRNAs are secreted actively through small vesicles called “exosomes” that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced. Here we demonstrate that miRNAs secreted by EBV-infected cells are transferred to and act in uninfected recipient cells. Using a quantitative RT-PCR approach, we demonstrate that mature EBV-encoded miRNAs are secreted by EBV-infected B cells through exosomes. These EBV-miRNAs are functional because internalization of exosomes by MoDC results in a dose-dependent, miRNA-mediated repression of confirmed EBV target genes, including\n                    <jats:italic>CXCL11/ITAC</jats:italic>\n                    , an immunoregulatory gene down-regulated in primary EBV-associated lymphomas. We demonstrate that throughout coculture of EBV-infected B cells EBV-miRNAs accumulate in noninfected neighboring MoDC and show that this accumulation is mediated by transfer of exosomes. Thus, the exogenous EBV-miRNAs transferred through exosomes are delivered to subcellular sites of gene repression in recipient cells. Finally, we show in peripheral blood mononuclear cells from patients with increased EBV load that, although EBV DNA is restricted to the circulating B-cell population, EBV BART miRNAs are present in both B-cell and non-B-cell fractions, suggestive of miRNA transfer. Taken together our findings are consistent with miRNA-mediated gene silencing as a potential mechanism of intercellular communication between cells of the immune system that may be exploited by the persistent human γ-herpesvirus EBV.\n                  </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380576197966255240","@type":"Researcher","foaf:name":[{"@value":"D. Michiel Pegtel"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Cancer Center Amsterdam, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255238","@type":"Researcher","foaf:name":[{"@value":"Katherine Cosmopoulos"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Tufts University School of Medicine, Boston, MA 02111;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255239","@type":"Researcher","foaf:name":[{"@value":"David A. Thorley-Lawson"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Tufts University School of Medicine, Boston, MA 02111;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255237","@type":"Researcher","foaf:name":[{"@value":"Monique A. J. van Eijndhoven"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Cancer Center Amsterdam, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255236","@type":"Researcher","foaf:name":[{"@value":"Erik S. Hopmans"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Cancer Center Amsterdam, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255235","@type":"Researcher","foaf:name":[{"@value":"Jelle L. Lindenberg"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Oncology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255232","@type":"Researcher","foaf:name":[{"@value":"Tanja D. de Gruijl"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Oncology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255234","@type":"Researcher","foaf:name":[{"@value":"Thomas Würdinger"}],"jpcoar:affiliationName":[{"@value":"Neuro-oncology Research Group, Department of Neurosurgery, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands; and"},{"@value":"Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical school, Boston MA 02115"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576197966255233","@type":"Researcher","foaf:name":[{"@value":"Jaap M. Middeldorp"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Cancer Center Amsterdam, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands;"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2010-03-18","prism:volume":"107","prism:number":"14","prism:startingPage":"6328","prism:endingPage":"6333"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0914843107"}],"createdAt":"2010-03-18","modifiedAt":"2022-04-12","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050017965004810880","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Extracellular-Vesicle Catch-and-Release Isolation System Using a Net-Charge Invertible Curvature-Sensing Peptide"}]},{"@id":"https://cir.nii.ac.jp/crid/1050025031476703872","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Infection of Epstein–Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines"}]},{"@id":"https://cir.nii.ac.jp/crid/1050025031479376384","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Adiponectin is partially associated with exosomes in mouse serum"}]},{"@id":"https://cir.nii.ac.jp/crid/1050025031481155072","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1050296420565128192","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Structural factors governing binding of curvature-sensing peptides to bacterial extracellular vesicles covered with hydrophilic polysaccharide chains"}]},{"@id":"https://cir.nii.ac.jp/crid/1050587981433165824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells"},{"@value":"Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveolae-dependent endocytosis and promote phenotypic modulation in target cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002215253793920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Interactions between cancer cells and normal cells via miRNAs in extracellular vesicles"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002217144242048","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Competitive Interactions of Cancer Cells and Normal Cells via Secretory MicroRNAs"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002219428550144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Profiling of Circulating MicroRNAs after a Bout of Acute Resistance Exercise in Humans"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004232064468992","@type":"Article","resourceType":"学術雑誌論文(journal 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article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Evaluation of desialylation effect on zeta potential of extracellular vesicles secreted from human prostate cancer cells by on-chip microcapillary electrophoresis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285705857641344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Gastritis-Infection-Cancer Sequence of Epstein-Barr Virus-Associated Gastric Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285708512306048","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285711737514112","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285711778144128","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Passive carriage of rabies virus by dendritic cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285712611566720","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein–Barr Virus-associated gastric carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714455025152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360286991106194560","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Where does the cargo go?: Solutions to provide experimental support for the “extracellular vesicle cargo transfer hypothesis”"}]},{"@id":"https://cir.nii.ac.jp/crid/1360286993316970752","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications"}]},{"@id":"https://cir.nii.ac.jp/crid/1360290617732350720","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Engineering exosome polymer hybrids by atom transfer radical polymerization"}]},{"@id":"https://cir.nii.ac.jp/crid/1360294809100000256","@type":"Article","resourceType":"学術雑誌論文(journal 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microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181473537792","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Small RNA as a regulator of hematopoietic development, immune response in infection and tumorigenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567182504371200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Multifunctional non-coding Epstein–Barr virus encoded RNAs (EBERs) contribute to viral pathogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567186528632064","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Establishment of a simpler method for measuring HDL-microRNAs"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567186781270144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567187485658880","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Cell Infectivity in Relation to Bovine Leukemia Virus gp51 and p24 in Bovine Milk Exosomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567189449260288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Analysis of Extracellular Vesicles in Gastric Juice from Gastric Cancer Patients"}]},{"@id":"https://cir.nii.ac.jp/crid/1360572092417440640","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pathophysiology of Preeclampsia: The Role of Exosomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360572092577364992","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380151696256","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Review of Basic Research about Ossification of the Spinal Ligaments Focusing on Animal Models"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846640945681280","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846642302353408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848658063360768","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Host Cell Prediction of Exosomes Using Morphological Features on Solid Surfaces Analyzed by Machine Learning"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848661277732096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Impact of Extracellular Vesicle-Encapsulated Circulating MicroRNAs in Lung Cancer Research"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848664372997888","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Herpesviral microRNAs in Cellular Metabolism and Immune Responses"}]},{"@id":"https://cir.nii.ac.jp/crid/1360850167454094080","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567364587648","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Extracellular vesicles: Their emerging roles in the pathogenesis of respiratory diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567441913088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumors Using Nanowire Scaffolds"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567541998464","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Exosomes of Epstein-Barr Virus-Associated Gastric Carcinoma Suppress Dendritic Cell Maturation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567669723264","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Development of a Simple and Rapid Method for In Situ Vesicle Detection in Cultured Media"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593756564096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Exosome-derived small non-coding RNAs reveal immune response upon grafting transplantation in\n                    <i>Pinctada fucata</i>\n                    (Mollusca)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861707133163264","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Extracellular vesicles in bone homeostasis: key roles of physiological and pathological conditions"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519612844288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Extracellular Vesicles in Cancer Metastasis: Potential as Therapeutic Targets and Materials"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233270903903232","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Biology of extracellular vesicles secreted from senescent cells as senescence‐associated secretory phenotype 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