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dc.contributor.authorO'Hara, Bethany A.
dc.contributor.authorMorris-Love, Jenna
dc.contributor.authorGee, Gretchen V.
dc.contributor.authorHaley, Sheila A.
dc.contributor.authorAtwood, Walter J.
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:13Z
dc.date.available2022-08-23T16:49:13Z
dc.date.issued2020-03-04
dc.date.submitted2020-04-16
dc.identifier.citation<p>O'Hara BA, Morris-Love J, Gee GV, Haley SA, Atwood WJ. JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor. PLoS Pathog. 2020 Mar 4;16(3):e1008371. doi: 10.1371/journal.ppat.1008371. PMID: 32130281; PMCID: PMC7075641. <a href="https://doi.org/10.1371/journal.ppat.1008371">Link to article on publisher's site</a></p>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1008371
dc.identifier.pmid32130281
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41416
dc.description.abstractThe human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV is common and the virus establishes a long-term persistent infection in the urogenital system of 50-70% of the human population worldwide. A major gap in the field is that we do not know how the virus traffics from the periphery to the brain to cause disease. Our recent discovery that human choroid plexus epithelial cells are fully susceptible to virus infection together with reports of JCPyV infection of choroid plexus in vivo has led us to hypothesize that the choroid plexus plays a fundamental role in this process. The choroid plexus is known to relay information between the blood and the brain by the release of extracellular vesicles. This is particularly important because human macroglia (oligodendrocytes and astrocytes), the major targets of virus infection in the central nervous system (CNS), do not express the known attachment receptors for the virus and do not bind virus in human tissue sections. In this report we show that JCPyV infected choroid plexus epithelial cells produce extracellular vesicles that contain JCPyV and readily transmit the infection to human glial cells. Transmission of the virus by extracellular vesicles is independent of the known virus attachment receptors and is not neutralized by antisera directed at the virus. We also show that extracellular vesicles containing virus are taken into target glial cells by both clathrin dependent endocytosis and macropinocytosis. Our data support the hypothesis that the choroid plexus plays a fundamental role in the dissemination of virus to brain parenchyma.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32130281&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright: © 2020 O’Hara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectVesicles
dc.subjectChoroid plexus
dc.subjectEpithelial cells
dc.subjectCentral nervous system
dc.subjectAntibodies
dc.subjectCell immortalization
dc.subjectImmune serum
dc.subjectAstrocytes
dc.subjectBiological Phenomena, Cell Phenomena, and Immunity
dc.subjectCell Biology
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectNervous System
dc.subjectNervous System Diseases
dc.subjectVirology
dc.subjectVirus Diseases
dc.subjectViruses
dc.titleJC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume16
dc.source.issue3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5217&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4198
dc.identifier.contextkey17380829
refterms.dateFOA2022-08-23T16:49:13Z
html.description.abstract<p>The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV is common and the virus establishes a long-term persistent infection in the urogenital system of 50-70% of the human population worldwide. A major gap in the field is that we do not know how the virus traffics from the periphery to the brain to cause disease. Our recent discovery that human choroid plexus epithelial cells are fully susceptible to virus infection together with reports of JCPyV infection of choroid plexus in vivo has led us to hypothesize that the choroid plexus plays a fundamental role in this process. The choroid plexus is known to relay information between the blood and the brain by the release of extracellular vesicles. This is particularly important because human macroglia (oligodendrocytes and astrocytes), the major targets of virus infection in the central nervous system (CNS), do not express the known attachment receptors for the virus and do not bind virus in human tissue sections. In this report we show that JCPyV infected choroid plexus epithelial cells produce extracellular vesicles that contain JCPyV and readily transmit the infection to human glial cells. Transmission of the virus by extracellular vesicles is independent of the known virus attachment receptors and is not neutralized by antisera directed at the virus. We also show that extracellular vesicles containing virus are taken into target glial cells by both clathrin dependent endocytosis and macropinocytosis. Our data support the hypothesis that the choroid plexus plays a fundamental role in the dissemination of virus to brain parenchyma.</p>
dc.identifier.submissionpathoapubs/4198
dc.contributor.departmentMassBiologics
dc.source.pagese1008371


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Copyright: © 2020 O’Hara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2020 O’Hara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.