{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:51:07Z","timestamp":1782175867174,"version":"3.54.5"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["320030_179531"],"award-info":[{"award-number":["320030_179531"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012159","name":"Myelin Repair Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012159","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"crossref","award":["unrestricted grant"],"award-info":[{"award-number":["unrestricted grant"]}],"id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            JC polyomavirus (JCPyV) is an opportunistic virus that remains in a latent state in the kidneys and lymphoid organs of more than half of the human adult population. In rare cases of severe immune suppression, the virus is able to establish a lytic infection of glial cells in the brain, resulting in a debilitating, demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Because of the exceptional species and tissue specificity of the virus, appropriate models of JCPyV infection in the brain are lacking, thus hampering progress toward the development of novel antiviral strategies and biomarkers of disease activity. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Here, using human-induced pluripotent stem cell (hiPSC)-derived astrocytes coupled with a multiparametric approach, we show that (i) JCPyV readily infects and replicates in astrocytes, (ii) JCPyV strongly dysregulates the cell biology, and (iii) these results adequately reflect\n            <jats:italic>ex vivo<\/jats:italic>\n            findings. We perform an in-depth characterization of the effect of JCPyV on the cell proteome over time, demonstrating a strong dysregulation of the cell cycle and activation of the DNA damage response. Furthermore, we show that the proteomic signature observed for infected astrocytes is extended to extracellular vesicles, underlining their potential as a resource to gain valuable insights into JCPyV infection in the brain.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs). These data suggest that astrocyte-derived EVs found in body fluids might serve as a rich source of information relevant to JCPyV infection in the brain, opening avenues toward better understanding the pathogenesis of the virus and, ultimately, the identification of new antiviral targets.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02751-23","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T13:01:18Z","timestamp":1696942878000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles"],"prefix":"10.1128","volume":"11","author":[{"given":"Larise","family":"Oberholster","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3604-5096","authenticated-orcid":false,"given":"Amandine","family":"Mathias","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Perriot","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Blaser","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Canales","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Culebras","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"},{"name":"Department of Psychiatry, Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Gimenez","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Laboratory of Neuroimmunology, Neuroscience Research Centre, Lausanne University Hospital (CHUV) and University of Lausanne , Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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