Multiple pathways to induction of virus-induced autoimmune demyelination: lessons from Theiler's virus infection

Journal of Autoimmunity
Stephen D MillerJ L Croxford

Abstract

Infection of SJL mice with wild-type BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) leads to CD4(+)T cell-mediated CNS demyelination characterized by the development of anti-myelin epitope autoimmune responses via epitope spreading during the chronic stage of disease. To exmine the feasibility of virus-encoded mimic epitopes to initiate CNS autoimmunity, we recently developed a molecular mimicry model of virus-induced demyelinating disease wherein a non-pathogenic variant strain of TMEV was engineered to encode a 30-mer peptide encompassing the immunodominant myelin proteolipid protein, PLP139-151, epitope. SJL mice infected intracerebrally with TMEV encoding either the native PLP139-151 determinant or various peptide mimics of the epitope develop an early onset demyelinating disease mediated by activated PLP139-151-specific Th1 cells. The autoimmune nature of this early-onset demyelinating disease is shown by the fact that induction of tolerance to the PLP139-151 peptide prevents clinical disease and associated PLP139-151-specific T cell responses without affecting T cell reactivity to virus epitopes. Most significantly, TMEV encoding a molecular mimic peptide derived from the Haemophilus influenzae bacteria, h...Continue Reading

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Citations

Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thomas CalzasciaTak W Mak
Nov 14, 2014·Journal of Neuroinflammation·Chittappen K PrajeethMartin Stangel
Mar 20, 2012·Best Practice & Research. Clinical Rheumatology·Cezar Augusto Muniz Caldas, Jozélio Freire de Carvalho
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Jun 5, 2010·International Reviews of Immunology·Simonetta Salemi, Raffaele D'Amelio
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Nov 13, 2015·Journal of Neuroinflammation·Carine SavarinStephen A Stohlman
Jul 1, 2004·The Annals of Otology, Rhinology, and Laryngology·Elias ToubiMichal Luntz
Aug 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julie K OlsonStephen D Miller
Mar 30, 2016·Current Opinion in Neurology·Xuan-Hung NguyenRoland S Liblau

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