Skip to main content

Advertisement

Log in

JC virus viremia in interferon-β-treated and untreated Italian multiple sclerosis patients and healthy controls

  • Short Communication
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Following the development of progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis (MS) patients treated with natalizumab and interferon-β (IFNβ), a possible correlation between JC virus (JCV), the etiological agent of PML, and MS has received heightened interest. In particular, attention has focused on assessing whether IFNβ treatment could affect the replication of JCV and thus its frequency in the peripheral blood of MS patients and whether the presence of JCV DNA in peripheral blood could be a predictive marker of the risk of developing PML. In order to answer to these questions, peripheral blood samples were collected from 59 INFβ-treated, 39 untreated relapsing-remitting MS patients, and 98 healthy controls (HCs) and JCV DNA levels were determined and quantified by means of a real-time polymerase chain reaction (Q-PCR) assay. Overall, no differences were found in the presence or viral load of JCV DNA of MS patients and the HCs, but JCV DNA was significantly less frequent in the peripheral blood of IFNβ-treated patients (13.6%) compared to the untreated MS patients (46.1%) and the healthy controls (28.6%). These results suggest that the presence of JCV in the blood of MS patients cannot be considered as a marker or a risk factor for PML development. In addition, they indicate that treatment with INFβ can lead to the reduction of presence of the JCV genome in the peripheral blood of MS patients and, thus, that this drug probably does not increase the risk of PML in MS patients treated with IFNβ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Reference

  • Alvarez-Lafuente R, De Las Heras V, Bartolome M, Picazo JJ, Arroyo R (2004). Beta-interferon treatment reduces human herpesvirus-6 viral load in multiple sclerosis relapses but not in remission. Eur Neurol 52: 87–91.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Buckle GJ, Godec MS, Rubi JU, Tornatore C, Major EO, Gibbs CJ Jr, Gajdusek DC, Asher DM (1992). Lack of JC viral genomic sequences in multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol 32: 829–831.

    Article  CAS  PubMed  Google Scholar 

  • Caldarelli-Stefano R, Vago L, Omodeo-Zorini E, Mediati M, Losciale L, Nebuloni M, Costanzi G, Ferrante P (1999). Detection and typing of JC virus in autopsy brains and extraneural organs of AIDS patients and non-immunocompromised individuals. J NeuroVirol 5: 125–133.

    Article  CAS  PubMed  Google Scholar 

  • Delbue S, Sotgiu G, Fumagalli D, Valli M, Borghi E, Mancuso R, Marchioni E, Maserati R, Ferrante P (2005). A case of a PML patient with four different JC virus TCR rearrangements in CSF, blood, serum and urine. J NeuroVirol 11: 51–57.

    Article  CAS  PubMed  Google Scholar 

  • Dorries K, Vogel E, Gunther S, Czub S (1994). Infection of human polyomaviruses JC and BK in peripheral blood leukocytes from immunocompetent individuals. Virology 198: 59–70.

    Article  CAS  PubMed  Google Scholar 

  • Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E, Cagni AE, Cocchi L, Suter F, Maserati R (1997). Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy. J Med Virol 52: 235–242.

    Article  CAS  PubMed  Google Scholar 

  • Ferrante P, Omodeo-Zorini E, Caldarelli-Stefano R, Mediati M, Fainardi E, Granieri E, Caputo D (1998). Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis patients. Mult Scler 4: 49–54.

    CAS  PubMed  Google Scholar 

  • Granieri E, Casetta I, Tola MR, Ferrante P (2001). Multiple Sclerosis: infectious hypothesis. Neurol Sci 22: 179–185.

    Article  CAS  PubMed  Google Scholar 

  • Hong J, Tejada-Simon MV, Rivera VM, Zang YC, Zhang JZ (2002). Anti-viral properties of interferon beta treatment in patients with multiple sclerosis. Mult Scler 8: 237–242.

    Article  CAS  PubMed  Google Scholar 

  • Kleinschmidt-DeMasters BK, Tyler KL (2005). Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 353: 369–374.

    Article  CAS  PubMed  Google Scholar 

  • Langer-Gould A, Atlas SW, Bollen AW, Pelletier D (2005). Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 35: 375–381.

    Article  Google Scholar 

  • Monaco MC, Atwood WJ, Gravell M, Tornatore CS, Major EO (1996). JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. J Virol 70: 7004–7012.

    CAS  PubMed  Google Scholar 

  • Monaco MC, Jensen PN, Hou J, Durham LC, Major EO (1998). Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol 72: 9918–9923.

    CAS  PubMed  Google Scholar 

  • Olmos Y, Alvarez-lafuente R, Garcia-Montojo M, Bartolomè V, Arroyo R (2005). JC virus and multiple sclerosis: a study in cerebrospinal fluid samples of multiple sclerosis patients at the first demyelinating event. Mult Scler 11(Suppl): S133-S134.

    Google Scholar 

  • Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971). Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1: 1257–1260.

    Article  CAS  PubMed  Google Scholar 

  • Pietropaolo V, Fioriti D, Mischitelli M, Anzivino E, Santini M, Millefiorini E, Di Rezze S, Degener AM (2005). Detection of human herpesviruses and polyomaviruses DNA in a group of patients with relapsing-remitting multiple sclerosis. New Microbiol 28: 199–203.

    CAS  PubMed  Google Scholar 

  • Rieckmann P, Michel U, Kehrl JH (1994). Regulation of JC virus expression in B lymphocytes. J Virol 68: 217–222.

    CAS  PubMed  Google Scholar 

  • Rudick RA, Ransohoff RM, Lee JC, Peppler R, Yu M, Mathisen PM, Tuohy VK (1998). In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis. Neurology 50: 1294–1300.

    CAS  PubMed  Google Scholar 

  • Stoner GL (1991). Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS. Acta Neurol Scand 83: 20–33.

    Article  CAS  PubMed  Google Scholar 

  • Tornatore C, Berger JR, Houff SA, Curfman B, Meyers K, Winfield D, Major EO (1992). Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy. Ann Neurol 31: 454–462.

    Article  CAS  PubMed  Google Scholar 

  • Walker DL, Padgett BL (1983). The epidemiology of human polyomaviruses. In Polyomaviruses and human neurological disease. Sever JL, Madden D (eds). New York: Alan R. Liss, pp 99–106.

    Google Scholar 

  • Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue EW, Jager HR, Clifford DB (2006) Evaluation of patients treated with Natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2: 924–933.

    Article  Google Scholar 

  • Zu Rhein GM (1967). Polyoma-like virions in a human demyelinating disease. Acta Neuropathol (Berl) 6: 57–68.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pasquale Ferrante.

Additional information

This work was supported by NIH grant MH072528 and by a grant from the Italian Ministry of Health (ISS 2004) awarded to PF.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delbue, S., Guerini, F.R., Mancuso, R. et al. JC virus viremia in interferon-β-treated and untreated Italian multiple sclerosis patients and healthy controls. Journal of NeuroVirology 13, 73–77 (2007). https://doi.org/10.1080/13550280601094563

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280601094563

Keywords

Navigation