nach oben

Erschienen in:

03.11.2016

JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab

verfasst von: Elena Uleri, Gabriele Ibba, Claudia Piu, Maurizio Caocci, Stefania Leoni, Giannina Arru, Caterina Serra, GianPietro Sechi, Antonina Dolei

Erschienen in: Journal of NeuroVirology | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Natalizumab is effective against multiple sclerosis (MS), but is associated with progressive multifocal leukoencephalopathy (PML), fatal disease caused by the JCV polyomavirus. The SF2/ASF (splicing factor2/alternative splicing factor) inhibits JCV in glial cells. We wondered about SF2/ASF modulation in the blood of natalizumab-treated patients and if this could influence JCV reactivation. Therefore, we performed a longitudinal study of MS patients under natalizumab, in comparison to patients under fingolimod and to healthy blood donors. Blood samples were collected at time intervals. The expression of SF2/ASF and the presence and expression of JCV in PBMC were analyzed. A bell-shaped regulation of SF2/ASF was observed in patients treated with natalizumab, increased in the first year of therapy, and reduced in the second one, while slightly changed, if any, in patients under fingolimod. Notably, SF2/ASF was up-regulated, during the first year, only in JCV DNA-positive patients, or with high anti-JCV antibody response; the expression of the JCV T-Ag protein in circulating B cells was inversely related to SF2/ASF protein expression. The SF2/ASF reduction, parallel to JCV activation, during the second year of therapy with natalizumab, but not with fingolimod, may help explain the increased risk of PML after the second year of treatment with natalizumab, but not with fingolimod. We propose that SF2/ASF has a protective role against JCV reactivation in MS patients. This study suggests new markers of disease behavior and, possibly, help in re-evaluations of therapy protocols.

685 cases (682 MS, 3 CD), as of September 7, 2016 (http://chefarztfrau.de/?page_id=716, accessed October 19, 2016). At the time of writing, three PML cases were reported in Natalizumab-naïve Fingolimod-treated patients, with doubts for diagnosis and/or treatments (Faulkner 2015).

For two patients the JCV DNA could not be evaluated, for scarcity of the samples.

The other two patients were anti-JCV antibody-negative, but the JCV DNA could not be evaluated.

Arru G, Leoni S, Pugliatti M, Mei A, Serra C, Delogu LG, Manetti R, Dolei A, Sotgiu S, Mameli G (2014) Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study. Mult Scler 20:174–182CrossRefPubMed

Atwood WJ, Amemiya K, Traub R, Harms J, Major EO (1992) Interaction of the human polyomavirus, JCV, with human B-lymphocytes. Virology 190:716–723CrossRefPubMed

Baroncini D, Ghezzi A, Annovazzi PO, Colombo B, Martinelli V, Minonzio G, Moiola L, Rodegher M, Zaffaroni M, Comi G (2016) Natalizumab versus fingolimod in patients with relapsing-remitting multiple sclerosis non-responding to first-line injectable therapies. Mult Scler 22:1315–1326

Berger JR, Fox RJ (2016) Reassessing the risk of natalizumab-associated PML. J Neurovirol 22:533–535CrossRefPubMed

Bloomgren G, Richman S, Hotermans C, Subramanyan M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C (2012) Risk of Natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 366:1870–1880CrossRefPubMed

Boldorini R, Caldarelli-Stefano R, Monga G, Zocchi M, Mediati M, Tosoni A, Ferrante P (1998) PCR detection of JC virus DNA in the brain tissue of a 9-year-old child with pleomorphic xanthoastrocytoma. J Neurovirol 4:242–245CrossRefPubMed

Capobianchi MR, Uleri E, Caglioti C, Dolei A (2015) Type I IFN family members: similarity, differences and interaction. Cytokine Growth Factor Rev 26:103–111CrossRefPubMed

Chalkias S, Dang X, Bord E, Stein MC, Kinkel RP, Sloane JA, Donnelly M, Ionete C, Houtchens MK, Buckle GJ, Batson S, Koralnik IJ (2014) JC virus reactivation during prolonged Natalizumab monotherapy for multiple sclerosis. Ann Neurol 75:925–934CrossRefPubMedPubMedCentral

Chapagain ML, Nerurkar VR (2010) Human polyomavirus JC (JCV) infection of human B lymphocytes: a possible mechanism for JCV transmigration across the blood-brain barrier. J Infect Dis 202:184–191CrossRefPubMedPubMedCentral

Chiarini M, Sottini A, Bertoli D, Serana F, Caimi L, Rasia S, Capra R, Imberti L (2015) Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients. Mult Scler 21:726–734CrossRefPubMed

Chun J, Hartung HP (2010) Mechanism of action of oral fingolimod in multiple sclerosis. Clin Neuropharmacol 33:91–101CrossRefPubMedPubMedCentral

Claes N, Dhaeze T, Fraussen J, Broux B, Van Wijmeersch B, Stinissen P, Hupperts R, Hellings N, Somers V (2014) Compositional changes of B and T cell subtypes during fingolimod treatment in multiple sclerosis patients: a 12-month follow-up study. PLoS One 9:e111115CrossRefPubMedPubMedCentral

Craddock J, Markovic-Plese S (2015) Immunomodulatory therapies for relapsing-remitting multiple sclerosis: monoclonal antibodies, currently approved and in testing. Expert Rev Clin Pharmacol 8:283–296CrossRefPubMed

Craigie M, Regan P, Otalora YL, Sariyer IK (2015) Molecular interplay between T-antigen and splicing factor, arginine/serine-rich 1 (SRSF1) controls JC virus gene expression in glial cells. Virol J 12:196CrossRefPubMedPubMedCentral

De Gascun CF, Carr MJ (2013) Human polyomavirus reactivation: disease pathogenesis and treatment approaches. Clin Dev Immunol 2013:373579

Dubey D, Cano CA, Stüve O (2016) Update on monitoring and adverse effects of approved second-generation disease-modifying therapies in relapsing forms of multiple sclerosis. Curr Opin Neurol 29:278–285CrossRefPubMed

Elsner C, Dörries K (1998) Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue. J Gen Virol 79:789–799CrossRefPubMed

Faulkner M (2015) Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf 14:1737–1748CrossRefPubMed

Frohman EM, Mc M, Remington G, Ryschkewitsch C, Jensen PN, Johnson K, Perkins M, Liebner J, Greenberg B, Monson N, Frohman TC, Douek D, Major EO (2014) JC virus in CD34+ and Cd19+ cells in patients with multiple sclerosis treated with Natalizumab. JAMA Neurol 71:596–602CrossRefPubMed

Gagne Brosseau MS, Stobbe G, Wundes A (2016) Natalizumab-related PML 2 weeks after negative anti-JCV antibody assay. Neurology 86:484–486CrossRefPubMed

Houff SA, Berger J (2010) The curious incident of the dog in the nighttime: does the absence of virus replication in Epstein-Barr virus-transformed B cells point to an important feature of JC virus biology? J Infect Dis 202:181–183CrossRefPubMed

Houff SA, Major EO, Katz DA, Kufta CV, Sever JL, Pittaluga S, Roberts JR, Gitt J, Saini N, Lux W (1988) Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy. N Engl J Med 318:301–305CrossRefPubMed

Kappos L, O’Connor PW, Polman CH, Vermersch P, Wiendl H, Pace A, Zhang A, Hotermans C (2013) Clinical effects of Natalizumab on multiple sclerosis appear early in treatment course. J Neurol 260:1388–1395CrossRefPubMedPubMedCentral

Koralnik IJ (2014) Finger pointing to JC virus: a tale of two indexes. Ann Neurol 76:789–791CrossRefPubMedPubMedCentral

Kornek B (2015) An update on the use of Natalizumab in the treatment of multiple sclerosis: appropriate patient selection and special considerations. Patient Prefer Adherence 9:675–684CrossRefPubMedPubMedCentral

Koudriavtseva T, Sbardella E, Trento E, Bordignon V, D’Agosto G, Cordiali-Fei P (2014) Long-term follow-up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with Natalizumab. Clin Exp Immunol 176:320–326CrossRefPubMedPubMedCentral

Kowalski CJ (1972) On the effects of non-normality on the distribution of the sample product-moment correlation coefficient. J R Stat Soc Ser C Appl Stat 1–12

Lindberg RLP, Achtnichts L, Hoffman F, Kuhle J, Kappos L (2008) Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. J Neuroimmunol 194:153–164CrossRefPubMed

Major EO, Frohman E, Douek D (2013) More on JC viremia in Natalizumab-treated patients with multiple sclerosis. N Engl J Med 369:1280CrossRefPubMed

Major EO (2011) History and current concepts in the pathogenesis of PML. Clev Clin J Med 78(2):S3–S7CrossRef

Mameli G, Madeddu G, Mei A, Uleri E, Poddighe L, Delogu LG, Maida I, Babudieri S, Serra C, Manetti R, Mura MS, Dolei A (2013) Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis? PLoS One 8:e78474CrossRefPubMedPubMedCentral

Manley JL, Tacke R (1996) SR proteins and splicing control. Genes Dev 10:1569–1579CrossRefPubMed

Marshall LJ, Ferenczy MW, Daley EL, Jensen PN, Ryschkewitsch CF, Major EO (2014) Lymphocyte gene expression and JC virus noncoding control region sequences are linked with the risk of progressive multifocal leukoencephalopathy. J Virol 88:5177–5183CrossRefPubMedPubMedCentral

Meira M, Sievers C, Hoffmann F, Haghikia A, Rasenack M, Décard BF, Kuhle J, Derfuss T, Kappos L, Lindberg RL (2016) Natalizumab-induced POU2AF1/Spi-B upregulation: a possible route for PML development. Neurol Neuroimmunol Neuroinflamm 3:e223CrossRefPubMedPubMedCentral

Monaco MC, Atwood WJ, Gravell M, Major EO (1996) JCV infection of hematopoietic progenitor cells, primary B lymphocytes and tonsillar stromal cells: implication for viral latency. J Virol 70:7004–7012PubMedPubMedCentral

Monaco MC, Major EO (2015) Immune system involvement in the pathogenesis of JC virus induced PML: what is learned from studies of patients with underlying diseases and therapies as risk factors. Front Immunol 6:159CrossRefPubMedPubMedCentral

Padgett BL, Walker DL (1973) Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis 127:467–470CrossRefPubMed

Perkins MR, Ryschkewitsch C, Liebner JC, Monaco MC, Himelfarb D, Ireland S, Roque A, Edward HL, Jensen PN, Remington G, Abraham T, Abraham J, Greenberg B, Kaufman C, LaGanke C, Monson NL, Xu X, Frohman E, Major EO, Douek DC (2012) Changes in JC virus-specific T cell responses during Natalizumab treatment and in Natalizumab-associated progressive multifocal leukoencephalopathy. PLoS Pathog 8:e1003014CrossRefPubMedPubMedCentral

Pietropaolo V, Bellizzi A, Anzivino E, Iannetta M, Zingaropoli MA, Rodio DM, Morreale M, Pontecorvo S, Francia A, Vullo V, Palamara AT, Ciardi MR (2015) Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under Natalizumab treatment. J Neurovirol 21:653–665CrossRefPubMedPubMedCentral

Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, Schlain B, Campagnolo D, Belachew S, Ticho B (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 76:802–812CrossRefPubMed

Sariyer IK, Khalili K (2011) Regulation of human neurotropic JC virus replication by alternative splicing factor SF2/ASF in glial cells. PLoS One 6:e14630CrossRefPubMedPubMedCentral

Sariyer IK, Sariyer R, Otte J, Gordon J (2016a) Pur-alpha induces JCV gene expression and viral replication by suppressing SRSF1 in glial cells. PLoS One 11:e0156819CrossRefPubMedPubMedCentral

Sariyer R, De Simone FI, Gordon J, Sariyer IK (2016b). Immune suppression of JC virus gene expression is mediated by SRSF1. J Neurovirol 22:597–606

Saure C, Warnke C, Zohren F, Schroeder T, Bruns I, Cadeddu RP, Weigelt C, Fischer U, Kobbe G, Hartung HP, Adams O, Kieseier BC, Haas R (2011) Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors. Arch Neurol 68:1428–1431CrossRefPubMed

Serra C, Biolchini A, Mei A, Kotenko S, Dolei A (2008) Type III and I interferons increase HIV uptake and replication in human cells that overexpress CD4, CCR5, and CXCR4. AIDS Res Hum Retrovir 24:173–180CrossRefPubMed

Shimoni-Sebag A, Lebenthal-Loinger I, Zender L, Karni R (2013) RRM1 domain of the splicing oncoprotein SRSF1 is required for MEK1-MAPK-ERK activation and cellular transformation. Carcinogenesis 34:2498–2504

Sinha R, Allemand E, Zhang Z, Karni R, Myers MP, Krainer AR (2010) Arginine methylation controls the subcellular localization and functions of the oncoprotein splicing factor SF2/ASF. Mol Cell Biol 30:2762–2774

Tan CS, Dezube BJ, Bhargava P, Autissier P, Wuthrich C, Miller J, Koralnik IJ (2009) Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation. J Infect Dis 199:881–888CrossRefPubMedPubMedCentral

Uleri E, Beltrami S, Gordon J, Dolei A, Sariyer IK (2011) Extinction of tumor antigen expression by SF2/ASF in JCV-transformed cells. Genes Cancer 2:728–736CrossRefPubMedPubMedCentral

Uleri E, Regan P, Dolei A, Sariyer IK (2013) SF2/ASF binding region within JC virus NCCR limits early gene transcription in glial cells. Virol J 10:147CrossRefPubMedPubMedCentral

Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, Verbeeck J, Geboes K, Robberecht W, Rutgeerts P (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353:362–368CrossRefPubMed

Van Schependom J, Gielen J, Laton J, Nagels G (2015) Assessing PML risk under immunotherapy: if all you have is a hammer, everything looks like a nail. Mult Scler 22:389–392

Viscidi RP, Khanna N, Tan CS, Li X, Jacobson L, Clifford DB, Nath A, Margolick JB, Shah KV, Hirsch HH, Koralnik IJ (2011) JC virus antibody and viremia as predictors of progressive multifocal leukoencephalopathy in human immunodeficiency virus-1-infected individuals. Clin Infect Dis 53:711–715CrossRefPubMedPubMedCentral

Vitaliti G, Matin N, Tabatabaie O, Di Traglia M, Pavone P, Lubrano R, Falsaperla R (2015) Natalizumab in multiple sclerosis: discontinuation, progressive multifocal leukoencephalopathy and possible use in children. Expert Rev Neurother 15:1321–1341CrossRefPubMed

Warnke C, Smolianov V, Dehmel T, Andrée M, Hengel H, Zohren F, Arendt G, Wiendl H, Haas R, Hartung HP, Adams O, Kieseier BC (2011) CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus. Mult Scler 17:151–156CrossRefPubMed

Wei G, Liu CK, Atwood WJ (2000) JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. J Neurovirol 6:127–136

White MK, Khalili K (2011) Pathogenesis of progressive multifocal leukoencephalopathy-revisited. J Infect Dis 203:578–586CrossRefPubMedPubMedCentral

White MK, Sariyer IK, Gordon J, Delbue S, Pietropaolo V, Berger JR, Khalili K (2016) Diagnostic assays for polyomavirus JC and progressive multifocal leukoencephalopathy. Rev Med Virol 26:102–114CrossRefPubMed

Wittmann T, Horowitz N, Benyamini N, Henig I, Zuckerman T, Rowe JM, Kra-Oz Z, Szwarcwort Cohen M, Oren I, Avivi I (2015) JC polyomavirus reactivation is common following allogeneic stem cell transplantation and its preemptive detection may prevent lethal complications. Bone Marrow Transplant 50:984–991CrossRefPubMed

Wollebo HS, Cotto B, Adiga R, Langford D, White MK (2016) Expression of signaling molecules in progressive multifocal leukoencephalopathy. Curr HIV Res 14:47–53CrossRefPubMedPubMedCentral

Wollebo HS, White MK, Gordon J, Berger JR, Khalili K (2015) Persistence and pathogenesis of the neurotropic polyomavirus JC. Ann Neurol 77:560–570CrossRefPubMedPubMedCentral

Zhao Y, Zhu T, Zhang X, Wang Q, Zhang J, Ji W, Ma Y (2015) Splicing factor 2/alternative splicing factor contributes to extracellular signal-regulated kinase activation in hepatocellular carcinoma cells. Mol Med Rep 12:3890–3894

Titel: JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab
verfasst von: Elena Uleri
Gabriele Ibba
Claudia Piu
Maurizio Caocci
Stefania Leoni
Giannina Arru
Caterina Serra
GianPietro Sechi
Antonina Dolei
Publikationsdatum: 03.11.2016
Verlag: Springer International Publishing
Erschienen in: Journal of NeuroVirology / Ausgabe 2/2017
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-016-0492-x

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2017

A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication

Association of midlife smoking status with change in processing speed and mental flexibility among HIV-seropositive and HIV-seronegative older men: the Multicenter AIDS Cohort Study

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals

Pseudo-typed Semliki Forest virus delivers EGFP into neurons

Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie