{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:06:30Z","timestamp":1792595190944,"version":"4.5.0"},"reference-count":305,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurologic Disorders and Stroke","doi-asserted-by":"publisher","award":["R35 NS127217"],"award-info":[{"award-number":["R35 NS127217"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has \u201creemerged\u201d as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where\/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.<\/jats:p>","DOI":"10.3390\/v15102112","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:56:57Z","timestamp":1697623017000},"page":"2112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Polyomavirus Wakes Up and Chooses Neurovirulence"],"prefix":"10.3390","volume":"15","author":[{"given":"Arrienne B.","family":"Butic","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareef K.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-2841","authenticated-orcid":false,"given":"Aron E.","family":"Lukacher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Atkinson, A.L., and Atwood, W.J. 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