HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) CME: Take the course for this article: Volume 68, Number 13, March 27, 2007 Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khalili, K. Articles by Berger, J. R. Search for Related Content PubMed PubMed Citation Articles by Khalili, K. Articles by Berger, J. R.

Reactivation of JC virus and development of PML in patients with multiple sclerosis

From the Department of Neuroscience (K.K., M.K.W.), Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, Department of Neurology (F.L.), Mount Sinai School of Medicine, New York, NY, and Department of Neurology (J.R.B.), University of Kentucky College of Medicine, Lexington; and Don Gnocchi Foundation (P.F.), University of Milan, Italy.

Address correspondence and reprint requests to Dr. K. Khalili, Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 N. 12 St., 015-96, Rm. 203, Philadelphia, PA 19122; e-mail: kamel.khalili{at}temple.edu

The attention of researchers and clinicians specializing in both multiple sclerosis (MS) and JC virus (JCV), the etiologic agent of progressive multifocal leukoencephalopathy (PML), was rekindled by the development of PML in two patients with MS enrolled in a clinical trial of combination therapy with natalizumab (Tysabri) and interferon β-1A (Avonex) in recent years. PML had not been previously reported with either MS or treatment with interferon β alone. This occurrence of PML with 4β1-integrin inhibition in MS raised a number of issues in terms both of the scientific understanding of these diseases and for the future of immunomodulatory treatment for MS. In this review, we examine the current status of knowledge of the virus, its molecular biology, life cycle, and pathogenetic mechanisms, and how this relates to the basic science and clinical perspectives of MS. A better understanding of the specific steps from JCV infection to the development of PML is key to this issue. Other critical issues for further investigation include the role of 4β1-integrin inhibition by natalizumab in the re-expression of JCV from latent sites and in the inhibition of entry into the brain and peripheral sites.

Supported by the Office of the Provost of Temple University, the Don Gnocchi Foundation, and the National Multiple Sclerosis Society for their support.

Disclosure: Dr. Khalili has served as a paid consultant for Elan Pharmaceuticals. Dr. Khalili’s compensation, including speaking fee and travel expenses, exceeded $10,000. Dr. Berger has served as a paid consultant for Biogen-Idec, Serono, Berlex, Teva, and GlaxoSmithKline. Aggregate honoraria from Berlex and Serono exceeded $10,000. In addition, he has received a grant from Berlex that will pay out at approximately $90,000 when completed over a 2-year period. He does not receive any salary support from this award. He has given seminars for Pfizer, Berlex, and Teva. Dr. Lublin has served as the chair of the Natalizumab Phase III Study Safety Monitoring Committee and has served as a paid consultant for Biogen-Idec. Dr. Lublin received compensation in excess of $10,000 in 2005. He has received no payment in the last 12 months.

Received July 27, 2006. Accepted in final form November 20, 2006.

This article has been cited by other articles:

				K. Tan, S. Patel, N. Gandhi, F. Chow, J. Rumbaugh, and A. Nath Burden of neuroinfectious diseases on the neurology service in a tertiary care center Neurology, October 7, 2008; 71(15): 1160 - 1166. [Abstract] [Full Text] [PDF]

				J Verbeeck, G Van Assche, J Ryding, E Wollants, K Rans, S Vermeire, M R Pourkarim, M Noman, J Dillner, M Van Ranst, et al. JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy? Gut, October 1, 2008; 57(10): 1393 - 1397. [Abstract] [Full Text] [PDF]

				{blacktriangledown}Natalizumab for multiple sclerosis? DTB, September 1, 2008; 46(9): 69 - 72. [Abstract] [Full Text] [PDF]

				M. K. Racke Editorial: Challenges in developing new multiple sclerosis therapies Therapeutic Advances in Neurological Disorders, September 1, 2008; 1(2): 63 - 65. [PDF]

				H. Bonig, A. Wundes, and T. Papayannopoulou Response: More about multiple sclerosis, natalizumab, and CD34+ hematopoietic progenitors Blood, July 1, 2008; 112(1): 209 - 210. [Full Text] [PDF]

				N. Merabova, D. Kaniowska, R. Kaminski, S. L. Deshmane, M. K. White, S. Amini, A. Darbinyan, and K. Khalili JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis J. Virol., February 1, 2008; 82(3): 1558 - 1569. [Abstract] [Full Text] [PDF]

				E. J. Verschoor, M. J. Groenewoud, Z. Fagrouch, A. Kewalapat, S. van Gessel, M. J. L. Kik, and J. L. Heeney Molecular characterization of the first polyomavirus from a New World primate: squirrel monkey polyomavirus J. Gen. Virol., January 1, 2008; 89(1): 130 - 137. [Abstract] [Full Text] [PDF]

				R. Feuer Tickling the CD200 Receptor: A Remedy for Those Irritating Macrophages Am. J. Pathol., August 1, 2007; 171(2): 396 - 398. [Full Text] [PDF]