{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:37:22Z","timestamp":1778823442261,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"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":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","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":["Viruses"],"abstract":"<jats:p>Background: Progressive multifocal leukoencephalopathy (PML) caused by the JC virus is the main limitation to the use of disease modifying therapies for treatment of multiple sclerosis (MS). Methods: To assess the PML risk in course of ocrelizumab, urine and blood samples were collected from 42 MS patients at baseline (T0), at 6 (T2) and 12 months (T4) from the beginning of therapy. After JCPyV-DNA extraction, a quantitative-PCR (Q-PCR) was performed. Moreover, assessment of JCV-serostatus was obtained and arrangements\u2019 analysis of non-coding control region (NCCR) and of viral capsid protein 1 (VP1) was carried out. Results: Q-PCR revealed JCPyV-DNA in urine at all selected time points, while JCPyV-DNA was detected in plasma at T4. From T0 to T4, JC viral load in urine was detected, increased in two logarithms and, significantly higher, compared to viremia. NCCR from urine was archetypal. Plasmatic NCCR displayed deletion, duplication, and point mutations. VP1 showed the S269F substitution involving the receptor-binding region. Anti-JCV index and IgM titer were found to statistically decrease during ocrelizumab treatment. Conclusions: Ocrelizumab in JCPyV-DNA positive patients is safe and did not determine PML cases. Combined monitoring of ocrelizumab\u2019s effects on JCPyV pathogenicity and on host immunity might offer a complete insight towards predicting PML risk.<\/jats:p>","DOI":"10.3390\/v13091684","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T23:25:50Z","timestamp":1629933950000},"page":"1684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment"],"prefix":"10.3390","volume":"13","author":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Brazzini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Piacentini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Limongi","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, Telematic University, 00163 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Teresa","family":"Palamara","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"},{"name":"Laboratory Affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation, Department of Public Health and Infectious Diseases, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/00005072-198709000-00005","article-title":"Diagnosis of progressive multifocal leukoencephalopathy by brain biopsy with biotin labeled DNA: DNA in situ hybridization","volume":"46","author":"Aksamit","year":"1987","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1097\/00002030-198912000-00010","article-title":"A rapid method for in situ hybridization for viral DNA in brain biopsies from patients with AIDS","volume":"3","author":"Houff","year":"1989","journal-title":"AIDS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0140-6736(71)91777-6","article-title":"Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy","volume":"297","author":"Padgett","year":"1971","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1515\/hsz-2016-0345","article-title":"The biology of JC polyomavirus","volume":"398","author":"Assetta","year":"2017","journal-title":"Biol. Chem."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"20180301","DOI":"10.1098\/rstb.2018.0301","article-title":"Intra-patient viral evolution in polyomavirus-related diseases","volume":"374","author":"McIlroy","year":"2019","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1128\/jvi.69.9.5843-5848.1995","article-title":"Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur alpha in glial cells","volume":"69","author":"Chen","year":"1995","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/JVI.77.1.665-672.2003","article-title":"Regulation of human polyomavirus JC virus gene transcription by AP-1 in glial cells","volume":"77","author":"Sadowska","year":"2003","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.virol.2008.02.021","article-title":"Early growth response-1 protein is induced by JC virus infection and binds and regulates the JC virus promoter","volume":"375","author":"Romagnoli","year":"2008","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1080\/13550280390241188","article-title":"Identical rearranged forms of JC polyomavirus transcriptional control region in plasma and cerebrospinal fluid of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy","volume":"9","author":"Fedele","year":"2003","journal-title":"J. Neurovirol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1128\/jvi.64.6.3139-3143.1990","article-title":"Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals","volume":"64","author":"Yogo","year":"1990","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/brain\/81.1.93","article-title":"Progressive multifocal leuko-encephalopathy","volume":"81","author":"Mancall","year":"1958","journal-title":"Brain"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/rmv.710","article-title":"Progressive multifocal leukoencephalopathy: Clinical and molecular aspects","volume":"22","author":"Tavazzi","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1097\/00002030-199208000-00012","article-title":"Progressive multifocal leukoencephalopathy in HIV-1-infected children","volume":"6","author":"Berger","year":"1992","journal-title":"AIDS"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ana.24371","article-title":"Persistence and pathogenesis of the neurotropic polyomavirus JC","volume":"77","author":"Wollebo","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s002340050383","article-title":"Progressive multifocal leukoencephalopathy in an HIV-infected child","volume":"39","author":"Morriss","year":"1997","journal-title":"Neuroradiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/ana.24574","article-title":"Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant","volume":"79","author":"Jelcic","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/13550280390195298","article-title":"The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: Defining a consensus terminology","volume":"9","author":"Cinque","year":"2003","journal-title":"J. Neurovirol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1128\/JVI.02657-08","article-title":"JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy","volume":"83","author":"Khanna","year":"2009","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1212\/WNL.0b013e31820d8b0b","article-title":"Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease","volume":"76","author":"Garvey","year":"2011","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1007\/s00147-004-0779-3","article-title":"Progressive multifocal leukoencephalopathy in transplant recipients","volume":"17","author":"Shitrit","year":"2005","journal-title":"Transpl. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.pediatrneurol.2006.10.007","article-title":"JC virus granule cell neuronopathy in a child with CD40 ligand deficiency","volume":"36","author":"Hecht","year":"2007","journal-title":"Pediatr. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/00006454-199305000-00010","article-title":"Progressive multifocal leukoencephalopathy in a child with immunodeficiency and hyperimmunoglobulinemia M","volume":"12","author":"Redfearn","year":"1993","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1056\/NEJMoa051586","article-title":"Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn\u2019s disease","volume":"353","author":"Sciot","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/WCO.0b013e328360279f","article-title":"Progressive multifocal leukoencephalopathy in patients with multiple sclerosis","volume":"26","author":"Baldwin","year":"2013","journal-title":"Curr. Opin. Neurol."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1056\/NEJMoa051847","article-title":"Progressive multifocal leukoencephalopathy in a patient treated with natalizumab","volume":"353","author":"Atlas","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000109933","article-title":"Natalizumab: Targeting \u03b14-Integrins in multiple sclerosis","volume":"5","author":"Engelhardt","year":"2008","journal-title":"Neurodegener. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJMoa051782","article-title":"Progressive multifocal leukoencephalo-pathy complicating treatment with natalizumab and interferon beta-1a for multiplesclerosis","volume":"353","author":"Tyler","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1182\/blood-2008-10-186999","article-title":"Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: A report of 57 cases from the Research on Adverse Drug Events and Reports project","volume":"113","author":"Carson","year":"2009","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/14740338.2017.1250881","article-title":"Safety of monoclonal antibodies for the treatment of multiple sclerosis","volume":"16","author":"McGinley","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1182\/blood-2013-02-482570","article-title":"Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity","volume":"121","author":"Rudnicka","year":"2013","journal-title":"Blood"},{"key":"ref_35","first-page":"84","article-title":"B-cells in multiple sclerosis","volume":"13","author":"Duddy","year":"2006","journal-title":"Int. MS J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/14740338.2016.1198775","article-title":"Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA\u2019s adverse event reporting system","volume":"15","author":"Raisch","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1007\/s00415-018-8996-3","article-title":"Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients","volume":"265","author":"Baber","year":"2018","journal-title":"J. Neurol."},{"key":"ref_38","unstructured":"Genentech (2021, August 04). Ocrelizumab & PML. Available online: www.ocrelizumabinfo.com."},{"key":"ref_39","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_40","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_41","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_42","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_43","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0042-6822(91)90069-N","article-title":"Amplification and sequencing of the control regions of BK and JC virus from human urine by polymerase chain reaction","volume":"180","author":"Sundsfjord","year":"1991","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/infdis\/167.1.13","article-title":"Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and uninfected subjects","volume":"167","author":"Markowitz","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/jmv.1890390110","article-title":"BK virus antigenic variants: Sequence analysis within the capsid VP1 epitope","volume":"39","author":"Jin","year":"1993","journal-title":"J. Med. Virol."},{"key":"ref_46","unstructured":"(2021, August 04). ClustalW2\u2013Multiple Sequence Alignment. Available online: http:\/\/www.ebi.ac.uk\/Tools\/msa\/clustalw2\/."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1007\/s007050170023","article-title":"New JC virus (JCV) genotypes from papua new guinea and micronesia (type 8 and type 2E) and evolutionary analysis of 32 complete JCV genomes","volume":"146","author":"Jobes","year":"2001","journal-title":"Arch. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/bib\/bbn017","article-title":"MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences","volume":"9","author":"Kumar","year":"2008","journal-title":"Brief. Bioinform."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"566-e41","DOI":"10.1111\/ene.13906","article-title":"The spectrum of progressive multifocal leukoencephalopathy: A practical approach","volume":"26","author":"Bartsch","year":"2019","journal-title":"Eur. J. Neurol."},{"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":"141","DOI":"10.1016\/j.jcv.2013.02.002","article-title":"A second-generation ELISA (STRATIFY JCV\u2122 DxSelect\u2122) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification","volume":"57","author":"Lee","year":"2013","journal-title":"J. Clin. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1212\/NXI.0000000000000195","article-title":"Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values","volume":"3","author":"Schwab","year":"2016","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.25259\/SNI-4-2019","article-title":"Anti-John Cunningham virus antibody index levels in multiple sclerosis patients treated with rituximab, fingolimod, and dimethyl fumarate","volume":"10","author":"Farley","year":"2019","journal-title":"Surg. Neurol. Int."},{"key":"ref_54","unstructured":"Williamson, E., and Dobrowolski, J. (2018). Impact of Ocrelizumab Treatment on PML Risk Biomarkers, Consortium of Multiple Sclerosis Centers."},{"key":"ref_55","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_56","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_57","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_58","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_59","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_60","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1099\/vir.0.035832-0","article-title":"JC virus promoter\/enhancers contain TATA box-associated Spi-B-binding sites that support early viral gene expression in primary astrocytes","volume":"93","author":"Marshall","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1000368","DOI":"10.1371\/journal.pgen.1000368","article-title":"Adaptive mutations in the JC virus protein capsid are associated with progressive multifocal leukoencephalopathy (PML)","volume":"5","author":"Sunyaev","year":"2009","journal-title":"PLoS Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1099\/0022-1317-82-5-1221","article-title":"Genotypes of JC virus in East, Central and Southwest Europe","volume":"82","author":"Agostini","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1002\/jmv.25458","article-title":"Kidney graft failure induced by BKPyV replication despite a strong reduction of the immunosuppressive therapy","volume":"91","author":"Anselmo","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Prezioso, C., Bianchi, M., Obregon, F., Ciotti, M., Sarmati, L., Andreoni, M., Palamara, A.T., Pascarella, S., Moens, U., and Pietropaolo, V. (2020). Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217998"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jaut.2014.11.009","article-title":"Rituximab-associated hypogammaglobulinemia: Incidence, predictors and outcomes in patients with multi-system autoimmune disease","volume":"57","author":"Roberts","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2217\/fvl-2019-0050","article-title":"An overview on human polyomaviruses biology and related diseases","volume":"14","author":"Ciotti","year":"2019","journal-title":"Future Virol."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jocn.2017.08.006","article-title":"Anti-JCV antibody serostatus and longitudinal evaluation in a Portuguese Multiple Sclerosis population","volume":"45","author":"Correia","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1212\/WNL.0000000000002330","article-title":"Natalizumab-related PML 2 weeks after negative anti-JCV antibody assay","volume":"86","author":"Brosseau","year":"2016","journal-title":"Neurology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:51:32Z","timestamp":1760165492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,25]]},"references-count":69,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["v13091684"],"URL":"https:\/\/doi.org\/10.3390\/v13091684","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,25]]}}}