JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor
UMass Chan Affiliations
MassBiologicsDocument Type
Journal ArticlePublication Date
2020-03-04Keywords
VesiclesChoroid plexus
Epithelial cells
Central nervous system
Antibodies
Cell immortalization
Immune serum
Astrocytes
Biological Phenomena, Cell Phenomena, and Immunity
Cell Biology
Immunology of Infectious Disease
Immunopathology
Nervous System
Nervous System Diseases
Virology
Virus Diseases
Viruses
Metadata
Show full item recordAbstract
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.Source
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. Link to article on publisher's site
DOI
10.1371/journal.ppat.1008371Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41416PubMed ID
32130281Related Resources
Rights
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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1008371
Scopus Count
Collections
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.