EBV Infection and Multiple Sclerosis: Lessons from a Marmoset Model.
Multiple sclerosis (MS) is thought to be initiated by the interaction of genetic and environmental factors, eliciting an autoimmune attack on the central nervous system. Epstein-Barr virus (EBV) is the strongest infectious risk factor, but an explanation for the paradox between high infection prevalence and low MS incidence remains elusive. We discuss new data using marmosets with experimental autoimmune encephalomyelitis (EAE) - a valid primate model of MS. The findings may help to explain how a common infection can contribute to the pathogenesis of MS. We propose that EBV infection induces citrullination of peptides in conjunction with autophagy during antigen processing, endowing B cells with the capacity to cross-present autoantigen to CD8+CD56+T cells, thereby leading to MS progression.
Department of Immunobiology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands; University of Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands. Electronic address: hart@bprc.nl.
Bert A
BA
'tHart
Department of Immunobiology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Yolanda S
YS
Kap
Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, UK.
Elena
E
Morandi
University of Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands.
Jon D
JD
Laman
Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, UK; Department of Neurology, Nottingham University Hospitals National Health Service (NHS) Trust, Nottingham, UK.
Bruno
B
Gran
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002956:Citrulline / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008285:Major Histocompatibility Complex; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology
D002956:Citrulline
B cell; EAE; autoantigen; autophagy; citrullination; processing