Epstein-Barr virus in the multiple sclerosis brain: a controversial issue-report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria

• Published in: Brain (London, England : 1878) Vol. 134; no. 9; pp. 2772 - 2786
• Main Authors: Lassmann, Hans, Niedobitek, Gerald, Aloisi, Francesca, Middeldorp, Jaap M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2011
• Subjects: Austria; B-Lymphocytes - immunology; Biological and medical sciences; Brain - immunology; Brain - pathology; Brain - virology; Diagnosis, Differential; Education; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - pathology; Epstein-Barr Virus Infections - physiopathology; Gene Expression; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Humans; Medical sciences; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Multiple Sclerosis - physiopathology; Multiple Sclerosis - virology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Occasional Paper; RNA, Viral; Sensitivity and Specificity; Austria; Europe; EBV biology; Epstein-Barr virus; EBV detection in tissue; multiple sclerosis; Gammaherpesvirinae; Nervous system diseases; Multiple sclerosis; Herpesviridae; Central nervous system; Epstein Barr virus; Epstein―Barr virus; Medical screening; Inflammatory disease; Encephalon; Virus; Central nervous system disease
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awr197

Recent epidemiological and immunological studies provide evidence for an association between Epstein-Barr virus infection and multiple sclerosis, suggesting a role of Epstein-Barr virus infection in disease induction and pathogenesis. A key question in this context is whether Epstein-Barr virus-infected B lymphocytes are present within the central nervous system and the lesions of patients with multiple sclerosis. Previous studies on this topic provided highly controversial results, showing Epstein-Barr virus reactivity in B cells in the vast majority of multiple sclerosis cases and lesions, or only exceptional Epstein-Barr virus-positive B cells in rare cases. In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented here. This report summarizes the current knowledge of Epstein-Barr virus biology and shows that Epstein-Barr virus infection is highly complex. There are still major controversies, how to unequivocally identify Epstein-Barr virus infection in pathological tissues, particularly in situations other than Epstein-Barr virus-driven lymphomas or acute Epstein-Barr virus infections. It further highlights that unequivocal proof of Epstein-Barr virus infection in multiple sclerosis lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods.