{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:57:38Z","timestamp":1784383058919,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["SG-2018-12366194"],"award-info":[{"award-number":["SG-2018-12366194"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["RP118163D5757CA6"],"award-info":[{"award-number":["RP118163D5757CA6"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at T12, whereas it remained similar for the HC group (35\u201340%). Viremia first occurred 6 months after treatment in MS patients and increased after 12 months, whereas it was absent in HC. The viral load in urine and plasma from the MS cohort increased over time, mostly pronounced in natalizumab-treated patients, whereas it persisted in HC. The archetypal NCCR was detected in all positive urine, whereas mutations were observed in plasma-derived NCCRs resulting in a more neurotropic variant. The prevalence and miR-J1-5p copy number in MS urine and plasma dropped after treatment, whereas they remained similar in HC specimens. Viruria and miR-J1-5p expression did not correlate with anti-JCV index. In conclusion, analyzing JCPyV DNA and miR-J1-5p levels may allow monitoring JCPyV activity and predicting MS patients at risk of developing PML.<\/jats:p>","DOI":"10.3390\/jcm11020347","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8377-0742","authenticated-orcid":false,"given":"Carla","family":"Prezioso","sequence":"first","affiliation":[{"name":"IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies, 00163 Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-9130","authenticated-orcid":false,"given":"Marco","family":"Ciotti","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Brazzini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Piacentini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-5537","authenticated-orcid":false,"given":"Sara","family":"Passerini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-8417","authenticated-orcid":false,"given":"Doriana","family":"Landi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Gabri","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonella","family":"Zingaropoli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-8627","authenticated-orcid":false,"given":"Marco","family":"Iannetta","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Altieri","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-2961","authenticated-orcid":false,"given":"Antonella","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Limongi","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, Telematic University, 00163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girolama Alessandra","family":"Marfia","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"},{"name":"Unit of Neurology, IRCCS Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Ciardi","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1286-467X","authenticated-orcid":false,"given":"Claudio Maria","family":"Mastroianni","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8330-4381","authenticated-orcid":false,"given":"Anna Teresa","family":"Palamara","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, Laboratory Affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-5462","authenticated-orcid":false,"given":"Ugo","family":"Moens","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Health Sciences, University of Troms\u00f8\u2014The Arctic University of Norway, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5723-8886","authenticated-orcid":false,"given":"Valeria","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41582-018-0082-z","article-title":"Treatment of multiple sclerosis\u2014Success from bench to bedside","volume":"15","author":"Tintore","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/WCO.0000000000000561","article-title":"Disease-modifying treatments for early and advanced multiple sclerosis: A new treatment paradigm","volume":"31","author":"Giovannoni","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_3","first-page":"179","article-title":"John Cunningham virus: An overview on biology and disease of the etiological agent of the progressive multifocal leukoencephalopathy","volume":"41","author":"Pietropaolo","year":"2018","journal-title":"New Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0733-8619(18)31105-8","article-title":"Progressive multifocal leukoencephalopathy","volume":"2","author":"Brooks","year":"1984","journal-title":"Neurol. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.7326\/0003-4819-107-1-78","article-title":"Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases","volume":"107","author":"Berger","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa044397","article-title":"A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis","volume":"354","author":"Polman","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S1474-4422(10)70028-4","article-title":"Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: Lessons from 28 cases","volume":"9","author":"Clifford","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.msard.2017.01.006","article-title":"Classifying PML risk with disease modifying therapies","volume":"12","author":"Berger","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMoa1107829","article-title":"Risk of natalizumab-associated progressive multifocal leukoencephalopathy","volume":"366","author":"Bloomgren","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s13311-017-0557-4","article-title":"Ocrelizumab and Other CD20+ B-Cell-Depleting Therapies in Multiple Sclerosis","volume":"14","author":"Gelfand","year":"2017","journal-title":"Neurotherapeutics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1212\/WNL.0b013e3182a351fb","article-title":"L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients","volume":"81","author":"Schwab","year":"2013","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/rmv.1866","article-title":"Diagnostic assays for polyomavirus JC and progressive multifocal leukoencephalopathy","volume":"26","author":"White","year":"2016","journal-title":"Rev. Med. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Iannetta, M., Zingaropoli, M.A., Bellizzi, A., Morreale, M., Pontecorvo, S., D\u2019Abramo, A., Oliva, A., Anzivino, E., Lo Menzo, S., and D\u2019Agostino, C. (2016). Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160277"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/1479-5876-10-248","article-title":"JC virus detection and JC virus-specific immunity in natalizumab-treated multiple sclerosis patients","volume":"10","author":"Mancuso","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s13365-015-0338-y","article-title":"Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under natalizumab treatment","volume":"21","author":"Pietropaolo","year":"2015","journal-title":"J. Neurovirol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102008","DOI":"10.1016\/j.msard.2020.102008","article-title":"Which is the best PML risk stratification strategy in natalizumab-treated patients affected by multiple sclerosis?","volume":"41","author":"Prezioso","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Prezioso, C., Grimaldi, A., Landi, D., Nicoletti, C.G., Brazzini, G., Piacentini, F., Passerini, S., Limongi, D., Ciotti, M., and Palamara, A.T. (2021). Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment. Viruses, 13.","DOI":"10.3390\/v13091684"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/infdis\/jiq097","article-title":"Pathogenesis of progressive multifocal leukoencephalopathy\u2014Revisited","volume":"203","author":"White","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.mib.2010.05.017","article-title":"Viral miRNAs: Tools for immune evasion","volume":"13","author":"Boss","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kincaid, R.P., and Sullivan, C.S. (2012). Virus-encoded microRNAs: An overview and a look to the future. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R78","DOI":"10.1186\/gb-2013-14-7-r78","article-title":"A blood based 12-miRNA signature of Alzheimer disease patients","volume":"14","author":"Leidinger","year":"2013","journal-title":"Genome Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrendo.2013.86","article-title":"Circulating microRNAs as novel biomarkers for diabetes mellitus","volume":"9","author":"Guay","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fgene.2013.00116","article-title":"Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures","volume":"4","author":"Madhavan","year":"2013","journal-title":"Front. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature02871","article-title":"The functions of animal microRNAs","volume":"431","author":"Ambros","year":"2004","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA expression profiles classify human cancers","volume":"435","author":"Lu","year":"2005","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yoshikawa, F.S.Y., Teixeira, F.M.E., Sato, M.N., and Oliveira, L.M.D.S. (2019). Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?. Cells, 8.","DOI":"10.3390\/cells8060611"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/1743-422X-10-268","article-title":"The miRNA world of polyomaviruses","volume":"10","author":"Lagatie","year":"2013","journal-title":"Virol. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9823","DOI":"10.1128\/JVI.01144-08","article-title":"Evolutionarily conserved function of a viral microRNA","volume":"82","author":"Seo","year":"2008","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2015.01.019","article-title":"Expression of BKV and JCV encoded microRNA in human cerebrospinal fluid, plasma and urine","volume":"65","author":"Nummi","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1007\/s13365-017-0560-x","article-title":"JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients","volume":"23","author":"Basnyat","year":"2017","journal-title":"J. Neurovirol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s13365-015-0325-3","article-title":"Detection of JCPyV microRNA in blood and urine samples of multiple sclerosis patients under natalizumab therapy","volume":"21","author":"Giovannelli","year":"2015","journal-title":"J. Neurovirol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2015.06.104","article-title":"The JCPyV DNA load inversely correlates with the viral microrna expression in blood and cerebrospinal fluid of patients at risk of PML","volume":"70","author":"Rocca","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Link, A., Balaguer, F., Nagasaka, T., Boland, C.R., and Goel, A. (2014). MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100036"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1743-422X-11-41","article-title":"Circulating human microRNAs are not linked to JC polyomavirus serology or urinary viral load in healthy subjects","volume":"11","author":"Lagatie","year":"2014","journal-title":"Virol. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1743-422X-11-158","article-title":"Viral miRNAs in plasma and urine divulge JC polyomavirus infection","volume":"11","author":"Lagatie","year":"2014","journal-title":"Virol. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1898838","DOI":"10.1080\/20002297.2021.1898838","article-title":"Detection of polyomavirus microRNA-5p expression in saliva shortly after kidney transplantation","volume":"13","author":"Mamana","year":"2021","journal-title":"J. Oral. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1086\/597126","article-title":"Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors","volume":"199","author":"Egli","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S1474-4422(18)30040-1","article-title":"Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: A decade of lessons learned","volume":"17","author":"Major","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1056\/NEJMoa0904267","article-title":"Asymptomatic reactivation of JC virus in patients treated with natalizumab","volume":"361","author":"Chen","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2077","DOI":"10.1002\/rmv.2077","article-title":"Progressive multifocal leukoencephalopathy and anti-CD20 monoclonal antibodies: What do we know after 20 years of rituximab","volume":"29","author":"Focosi","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10846","DOI":"10.1128\/JVI.00542-09","article-title":"Regulation of gene expression in primate polyomaviruses","volume":"83","author":"White","year":"2009","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/(SICI)1096-9071(199607)49:3<199::AID-JMV7>3.0.CO;2-#","article-title":"Glial and muscle embryonal carcinoma cell-specific independent regulation of expression of human JC virus early promoter by cyclic AMP response elements and adjacent nuclear factor 1 binding sites","volume":"49","author":"Kumar","year":"1996","journal-title":"J. Med. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1007\/s00705-017-3542-7","article-title":"Efficient propagation of archetype JC polyomavirus in COS-7 cells: Evaluation of rearrangements within the NCCR structural organization after transfection","volume":"162","author":"Prezioso","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12985-020-1295-5","article-title":"JCPyV NCCR analysis in PML patients with different risk factors: Exploring common rearrangements as essential changes for neuropathogenesis","volume":"17","author":"Ciardi","year":"2020","journal-title":"Virol. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5297980","DOI":"10.1155\/2018\/5297980","article-title":"JC Virus-DNA Detection Is Associated with CD8 Effector Accumulation in Peripheral Blood of Patients with Multiple Sclerosis under Natalizumab Treatment, Independently from JC Virus Serostatus","volume":"2018","author":"Zingaropoli","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/ana.23893","article-title":"JC virus antibody status underestimates infection rates","volume":"74","author":"Berger","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/ana.20703","article-title":"Diagnostic criteria for multiple sclerosis: 2005 revisions to the \u201cMcDonald Criteria\u201d","volume":"58","author":"Polman","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/ana.24286","article-title":"Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy","volume":"76","author":"Plavina","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1002\/jmv.21313","article-title":"Presence and expression of JCV early gene large T antigen in the brains of immunocompromised and immunocompetent individuals","volume":"80","author":"Delbue","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12985-018-0939-1","article-title":"COS-7-based model: Methodological approach to study John Cunningham virus replication cycle","volume":"15","author":"Prezioso","year":"2018","journal-title":"Virol. J."},{"key":"ref_53","unstructured":"(2021, November 24). ClustalW2\u2013Multiple Sequence Alignment. Available online: http:\/\/www.ebi.ac.uk\/Tools\/msa\/clustalw2\/."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jviromet.2006.01.018","article-title":"Real-time, quantitative PCR assays for the detection of virus-specific DNA in samples with mixed populations of polyomaviruses","volume":"135","author":"Pal","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Takahashi, K., Sato, Y., Sekizuka, T., Kuroda, M., Suzuki, T., Hasegawa, H., and Katano, H. (2020). High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008523"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:14:54Z","timestamp":1760364894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["jcm11020347"],"URL":"https:\/\/doi.org\/10.3390\/jcm11020347","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]}}}