Further evidence to link EBV virus infection with MS

Mon 30 Jun 2008

New research published in The Journal of Experimental Medicine has provided more evidence that a common human virus called Epstein Barr Virus (EBV) plays an important role in the development of MS.

EBV, the virus which causes glandular fever, has been linked to MS for over 30 years. Several studies appear to have shown that people with MS have been exposed to EBV and that EBV is active in their bodies during MS attacks.

In MS, lesions (or plaques) are patches in the central nervous system where inflammation has resulted in the loss of myelin, the protective sheath which surrounds nerve fibres. This study on 22 people with MS demonstrated that EBV is present in the lesions that attack myelin in almost all of the cases examined (21 out of 22).

The researchers propose that EBV is carried across the blood-brain barrier by a certain type of immune cell called B cells, the cells of the immune system that make antibodies. EBV infected B cells which accumulated in lesions were shown to be a common feature of MS, and the number of EBV infected cells correlated with the degree of brain inflammation.

The absence of EBV infected B cells in other inflammatory neurological conditions indicates that this may be specific to MS and not a general phenomenon driven by inflammation.

It is worth noting that EBV is one of the most common viruses in the environment, with up to 90 per cent of the population thought to have been infected by it at some time, most of whom do not go on to develop MS.

There is not yet enough data to prove that EBV infection causes MS. There needs to be further research to explain the link between EBV infection and MS.

Source 1
Source 2 (for date)


ARTICLE

Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain

Barbara Serafini¹, Barbara Rosicarelli¹, Diego Franciotta², Roberta Magliozzi³, Richard Reynolds³, Paola Cinque⁴, Laura Andreoni², Pankaj Trivedi⁵, Marco Salvetti⁶, Alberto Faggioni⁵, and Francesca Aloisi¹

¹ Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
² Laboratory of Neuroimmunology, IRCCS Neurological Institute C. Mondino University of Pavia, 27100 Pavia, Italy
³ Department of Cellular & Molecular Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital Campus, London W6 8RF, UK
⁴ Division of Infectious Diseases, San Raffaele Scientific Institute, 20127 Milano, Italy
⁵ Institute Pasteur-Cenci Bolognetti Foundation, Department of Experimental Medicine, University of Rome La Sapienza, 00161 Rome, Italy
⁶ Department of Neurology and Centro Neurologico Terapia Sperimentale (CENTERS), Ospedale S. Andrea, University of Rome La Sapienza, 00189 Rome, Italy

CORRESPONDENCE Francesca Aloisi: fos4@iss.it

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8⁺ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.

---

Abbreviations used: AID, activation-induced cytidine deaminase; CNS, central nervous system; CSF, cerebrospinal fluid; EBER, EBV-encoded small nuclear mRNA; EBNA, Epstein-Barr nuclear antigen; HHV-6, human herpesvirus 6; LMP, latency membrane protein; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; OCB, oligoclonal IgG band; RA, rheumatoid arthritis.

Source

Full Text

Perhaps a note to
Francesca Aloisi: fos4@iss.it
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
is indicated noting Nanoviricides' interest and capabilities suggesting a cooperative approach to remove EBV from the MS picture.