EBV Infection and Multiple Sclerosis: Lessons From a Marmoset Model

Trends Mol Med. 2016 Dec;22(12):1012-1024. doi: 10.1016/j.molmed.2016.10.007. Epub 2016 Nov 8.


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.

Keywords: B cell; EAE; autoantigen; autophagy; citrullination; processing.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Citrulline / immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / virology*
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunity, Cellular
  • Major Histocompatibility Complex
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / virology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • T-Lymphocytes / virology


  • Citrulline