Skip to main content

Advertisement

Log in

Disease-modifying drugs for multiple sclerosis and JC virus expression

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis (MS) occurred in two individuals also treated with interferon β1a, raising concerns about the interaction of these disease-modifying agents and leading to the recommendation to avoid their concomitant administration. However, type I interferons are antiviral. Using a real-time quantitative polymerase chain reaction for the detection and quantification of the John Cunningham virus (JCV), DNA in peripheral blood mononuclear cells (PBMCs), and urine in MS patients, we tested the hypothesis that MS disease-modifying drugs (DMD) qualitatively and quantitatively alter JCV prevalence and viral copy numbers. Two hundred thirty-nine patients were enrolled in a cross-sectional study in which blood and urine specimens were collected at a single time and 37 newly diagnosed, treatment-naïve MS patients were enrolled in a longitudinal study in which specimens were obtained at diagnosis and 6 months after treatment initiation. JCV DNA was detected in PBMCs of only two patients (0.07 %), but was commonly detected in the urine (46.8 %) in this population. There was no effect of DMDs on blood or urinary JCV prevalence or viral copy numbers with either glatiramer acetate (Copaxone®) or interferon-β therapy (Avonex®, Betaseron®, or Rebif®). The small number of patients on other therapies precluded meaningful comment about their effects. No obvious effect of the platform DMDs on JCV prevalence was observed even for the interferon-βs.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Alvarez-Lafuente R, Garcia-Montojo M et al (2007) Interferon-beta treatment and active replication of the JC virus in relapsing-remitting multiple sclerosis patients. Eur J Neurol 14(2):233–236

    Article  PubMed  CAS  Google Scholar 

  • Berger J, Pall L et al (1992) A pilot study of recombinant alpha 2a interferon in the treatment of AIDS-related progressive multifocal leukoencephalopathy (abstract). Neurology 42(Suppl 3):257

    Google Scholar 

  • Berger JR, Miller CS et al (2006) JC virus detection in bodily fluids: clues to transmission. Clin Infect Dis 43(1):e9–e12

    Article  PubMed  Google Scholar 

  • BiogenIdec (2011) PML incidence in patients receiving TYSABRI. https://medinfo.biogenidec.com/medinfo/secure/pmlresource.do?resource=TYSABRIPMLSafetyUpdate. Accessed 26 Nov 2011

  • Biron CA (1999) Initial and innate responses to viral infections—pattern setting in immunity or disease. Curr Opin Microbiol 2(4):374–381

    Article  PubMed  CAS  Google Scholar 

  • Chang H, Wang M et al (2002) High incidence of JC viruria in JC-seropositive older individuals. J Neurovirol 8(5):447–451

    Article  PubMed  CAS  Google Scholar 

  • Co JK, Verma S et al (2007) Interferon-alpha and -beta restrict polyomavirus JC replication in primary human fetal glial cells: implications for progressive multifocal leukoencephalopathy therapy. J Infect Dis 196(5):712–718

    Article  PubMed  CAS  Google Scholar 

  • Delbue S, Guerini FR et al (2007) JC virus viremia in interferon-beta-treated and untreated Italian multiple sclerosis patients and healthy controls. J Neurovirol 13(1):73–77

    Article  PubMed  CAS  Google Scholar 

  • Egli A, Infanti L et al (2009) Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 199(6):837–846

    Article  PubMed  CAS  Google Scholar 

  • Gorelik L, Lerner M et al (2010) Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 68(3):295–303

    Article  PubMed  Google Scholar 

  • Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol 7(2):131–137

    Article  PubMed  CAS  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(4):369–374

    Article  PubMed  CAS  Google Scholar 

  • Langer-Gould A, Atlas SW et al (2005) Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353(4):375–381

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie J, Wilson KS et al (2003) Association between simian virus 40 DNA and lymphoma in the United Kingdom. J Natl Cancer Inst 95(13):1001–1003

    Article  PubMed  CAS  Google Scholar 

  • Nath A, Venkataramana A et al (2006) Progression of progressive multifocal leukoencephalopathy despite treatment with beta-interferon. Neurology 66(1):149–150

    Article  PubMed  CAS  Google Scholar 

  • Pagani E, Delbue S et al (2003) Molecular analysis of JC virus genotypes circulating among the Italian healthy population. J Neurovirol 9(5):559–566

    PubMed  CAS  Google Scholar 

  • Polo C, Perez JL et al (2004) Prevalence and patterns of polyomavirus urinary excretion in immunocompetent adults and children. Clin Microbiol Infect 10(7):640–644

    Article  PubMed  CAS  Google Scholar 

  • Verma S, Ziegler K et al (2006) JC virus induces altered patterns of cellular gene expression: interferon-inducible genes as major transcriptional targets. Virology 345(2):457–467

    Article  PubMed  CAS  Google Scholar 

  • Yousry TA, Major EO et al (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354(9):924–933

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This study is supported by a grant to Dr. Berger from EMD Serono.

Disclosures

This study was supported by EMD Serono. Dr. Miller is on the editorial board of Oral Surgery Oral Medicine Oral Pathology and Endodontology. He has received grants from the National Institutes of Health and BeechTree Labs. Dr. Houff, Mr. Hopper, Dr. Danaher, Dr. Gurwell, Dr. Lin, and Ms. Vega report no disclosures. Dr. Berger is on the editorial board of the Journal of Neurovirology, MS and Related Disorders, ISRN Education, Neuroscience, and World Journal of Rheumatology. He has received grant support from BiogenIdec, the PML Consortium, Bayer, and EMD Serono. He has also served as a consultant to Bayer, BiogenIdec, GlaxoSmithKline, Eisai, Novartis, Millenium, and Genentech and has received speakers honoraria from Bayer, Teva, and BiogenIdec.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph R. Berger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miller, C.S., Houff, S.A., Hopper, J. et al. Disease-modifying drugs for multiple sclerosis and JC virus expression. J. Neurovirol. 18, 411–415 (2012). https://doi.org/10.1007/s13365-012-0107-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-012-0107-0

Keywords

Navigation