| Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation. | |
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MedLine Citation:
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PMID: 20535037 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A cardinal feature of multiple sclerosis (MS) is the persistent intrathecal synthesis of antibodies. Our previous finding that a large fraction of B cells infiltrating the MS brain are infected with Epstein-Barr virus (EBV) raises the possibility that this virus, because of its ability to establish a latent infection in B cells and interfere with their differentiation, contributes to B-cell dysregulation in MS. The aim of this study was to gain further insight into EBV latency programs and their relationship to B-cell activation in the MS brain. Immunohistochemical analysis of postmortem MS brain samples harboring large EBV deposits revealed that most B cells in white matter lesions, meninges, and ectopic B-cell follicles are CD27+ antigen-experienced cells and coexpress latent membrane protein 1 and latent membrane protein 2A, 2 EBV-encoded proteins that provide survival and maturation signals to B cells. By combining laser-capture microdissection with preamplification reverse transcription-polymerase chain reaction techniques, EBV latency transcripts (latent membrane protein 2A, EBV nuclear antigen 1) were detected in all MS brain samples analyzed. We also found that B cell-activating factor of the tumor necrosis factor family is expressed in EBV-infected B cells in acute MS lesions and ectopic B-cell follicles. These findings support a role for EBV infection in B-cell activation in the MS brain and suggest that B cell-activating factor of the tumor necrosis factor family produced by EBV-infected B cells may contribute to this process resulting in viral persistence and, possibly, disruption of B-cell tolerance. |
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Authors:
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Barbara Serafini; Martina Severa; Sandra Columba-Cabezas; Barbara Rosicarelli; Caterina Veroni; Giuseppe Chiappetta; Roberta Magliozzi; Richard Reynolds; Eliana Marina Coccia; Francesca Aloisi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neuropathology and experimental neurology Volume: 69 ISSN: 1554-6578 ISO Abbreviation: J. Neuropathol. Exp. Neurol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-07-19 Revised Date: 2012-12-07 |
Medline Journal Info:
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Nlm Unique ID: 2985192R Medline TA: J Neuropathol Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 677-93 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism B-Cell Activating Factor / metabolism* B-Lymphocytes / metabolism* Brain / cytology* Cell Line, Transformed Epstein-Barr Virus Infections / complications, pathology Epstein-Barr Virus Nuclear Antigens / metabolism Herpesvirus 4, Human / pathogenicity* Humans Microdissection / methods Microscopy, Confocal Multiple Sclerosis / complications, pathology*, virology* Postmortem Changes Viral Matrix Proteins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/B-Cell Activating Factor; 0/EBV-associated membrane antigen, Epstein-Barr virus; 0/EBV-encoded nuclear antigen 1; 0/Epstein-Barr Virus Nuclear Antigens; 0/TNFSF13B protein, human; 0/Viral Matrix Proteins |
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