title: Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain.
abstract: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Serafini
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosicarelli
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.forename: Roberta
authors.initials: R
authors.lastname: Magliozzi
authors.forename: Richard
authors.initials: R
authors.lastname: Reynolds
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Laura
authors.initials: L
authors.lastname: Andreoni
authors.forename: Pankaj
authors.initials: P
authors.lastname: Trivedi
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D006801:Humans; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D016019:Survival Analysis