{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:39:52Z","timestamp":1792633192150,"version":"4.5.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1003014","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T22:20:14Z","timestamp":1352413214000},"page":"e1003014","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy"],"prefix":"10.1371","volume":"8","author":[{"given":"Molly R.","family":"Perkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ryschkewitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Liebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara G.","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Himelfarb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ireland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelys","family":"Roque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L.","family":"Edward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Remington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaspreet","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Greenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"LaGanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Monson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Frohman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene O.","family":"Major","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"ref1","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":"1","author":"BL Padgett","year":"1971","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMoa1107829","article-title":"Risk of natalizumab-associated progressive multifocal leukoencephalopathy","volume":"366","author":"G Bloomgren","year":"2012","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S1474-4422(11)70149-1","article-title":"Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring","volume":"10","author":"L Kappos","year":"2011","journal-title":"Lancet Neurol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s11908-011-0196-6","article-title":"The changing landscape of progressive multifocal leukoencephalopathy","volume":"13","author":"S Kedar","year":"2011","journal-title":"Curr Infect Dis Rep"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1212\/WNL.0b013e3181a8266f","article-title":"Natalizumab treatment is associated with peripheral sequestration of proinflammatory T cells","volume":"72","author":"P Kivisakk","year":"2009","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.4049\/jimmunol.0803418","article-title":"Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis","volume":"182","author":"C Coisne","year":"2009","journal-title":"J Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.20858","article-title":"Immune surveillance in multiple sclerosis patients treated with natalizumab","volume":"59","author":"O Stuve","year":"2006","journal-title":"Ann Neurol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1056\/NEJMp0906248","article-title":"Reemergence of PML in natalizumab-treated patients\u2013new cases, same concerns","volume":"361","author":"EO Major","year":"2009","journal-title":"N Engl J Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1212\/WNL.30.3.256","article-title":"Progressive multifocal leukoencephalopathy (PML): in vitro cell-mediated immune responses to mitogens and JC virus","volume":"30","author":"E Willoughby","year":"1980","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1080\/13550280152537175","article-title":"JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy","volume":"7","author":"RA Du Pasquier","year":"2001","journal-title":"J Neurovirol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/00002030-200307040-00004","article-title":"Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy","volume":"17","author":"J Gasnault","year":"2003","journal-title":"AIDS"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4049\/jimmunol.168.1.499","article-title":"Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope","volume":"168","author":"IJ Koralnik","year":"2002","journal-title":"J Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1128\/JVI.75.7.3483-3487.2001","article-title":"JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy","volume":"75","author":"IJ Koralnik","year":"2001","journal-title":"J Virol"},{"key":"ref14","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":"N Khanna","year":"2009","journal-title":"J Virol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1093\/brain\/awh215","article-title":"A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathy","volume":"127","author":"RA Du Pasquier","year":"2004","journal-title":"Brain"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"7256","DOI":"10.1128\/JVI.02506-10","article-title":"Role of CD4+ and CD8+ T-cell responses against JC virus in the outcome of patients with progressive multifocal leukoencephalopathy (PML) and PML with immune reconstitution inflammatory syndrome","volume":"85","author":"S Gheuens","year":"2011","journal-title":"J Virol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"RA Seder","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/ana.1004","article-title":"Cellular and humoral immune response in progressive multifocal leukoencephalopathy","volume":"49","author":"F Weber","year":"2001","journal-title":"Ann Neurol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1468-1331.2009.02532.x","article-title":"The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers","volume":"16","author":"M Khademi","year":"2009","journal-title":"Eur J Neurol"},{"key":"ref20","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":"CH Polman","year":"2006","journal-title":"N Engl J Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMoa044396","article-title":"Natalizumab plus interferon beta-1a for relapsing multiple sclerosis","volume":"354","author":"RA Rudick","year":"2006","journal-title":"N Engl J Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jneuroim.2011.02.010","article-title":"Novel mechanisms of immune modulation of natalizumab in multiple sclerosis patients","volume":"235","author":"M Skarica","year":"2011","journal-title":"J Neuroimmunol"},{"key":"ref23","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":"Y Chen","year":"2009","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S1474-4422(10)70006-5","article-title":"Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study","volume":"9","author":"S Jilek","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm1492","article-title":"Interleukin-10 determines viral clearance or persistence in vivo","volume":"12","author":"DG Brooks","year":"2006","journal-title":"Nat Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1073\/pnas.0914500107","article-title":"IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection","volume":"107","author":"DG Brooks","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1615\/CritRevImmunol.v28.i2.40","article-title":"Immune responses against persistent viral infections: possible avenues for immunotherapeutic interventions","volume":"28","author":"S Fuse","year":"2008","journal-title":"Crit Rev Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cyto.a.21015","article-title":"SPICE: exploration and analysis of post-cytometric complex multivariate datasets","volume":"79","author":"M Roederer","year":"2011","journal-title":"Cytometry A"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/ana.22137","article-title":"JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab","volume":"68","author":"CF Ryschkewitsch","year":"2010","journal-title":"Ann Neurol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1474-4422(10)70124-1","article-title":"Discrepant findings in immune responses to JC virus in patients receiving natalizumab","volume":"9","author":"CS Tan","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S1474-4422(10)70125-3","article-title":"Discrepant findings in immune responses to JC virus in patients receiving natalizumab? Authors&apos; reply","volume":"9","author":"S Jilek","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1084\/jem.20092532","article-title":"IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform","volume":"207","author":"PA Darrah","year":"2010","journal-title":"J Exp Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"e42094","DOI":"10.1371\/journal.pone.0042094","article-title":"Ribavirin exerts differential effects on functions of cd4(+) Th1, th2, and regulatory T cell clones in hepatitis C","volume":"7","author":"B Langhans","year":"2012","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1365-3083.2006.01844.x","article-title":"Levels of IL-15 in serum and cerebrospinal fluid of patients with Behcet&apos;s disease","volume":"64","author":"K Hamzaoui","year":"2006","journal-title":"Scand J Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000287582","article-title":"Interleukin-15 and interleukin-12 are elevated in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis","volume":"63","author":"M Rentzos","year":"2010","journal-title":"Eur Neurol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jns.2005.10.003","article-title":"IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis","volume":"241","author":"M Rentzos","year":"2006","journal-title":"J Neurol Sci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1177\/0891988706286226","article-title":"IL-15 is elevated in cerebrospinal fluid of patients with Alzheimer&apos;s disease and frontotemporal dementia","volume":"19","author":"M Rentzos","year":"2006","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1046\/j.1365-2249.1998.00478.x","article-title":"IL-15 mRNA expression is up-regulated in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis (MS)","volume":"111","author":"P Kivisakk","year":"1998","journal-title":"Clin Exp Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ana.22128","article-title":"Anti-JC virus antibodies: implications for PML risk stratification","volume":"68","author":"L Gorelik","year":"2010","journal-title":"Ann Neurol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/13550280152537201","article-title":"Predicted amino acid sequences for 100 JCV strains","volume":"7","author":"CL Cubitt","year":"2001","journal-title":"J Neurovirol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3109\/13550289509113966","article-title":"Identification of three new JC virus proteins generated by alternative splicing of the early viral mRNA","volume":"1","author":"PW Trowbridge","year":"1995","journal-title":"J Neurovirol"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1003014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T15:23:57Z","timestamp":1540049037000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1003014"}},"subtitle":[],"editor":[{"given":"Michael J.","family":"Imperiale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,11,8]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1003014","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,8]]}}}