Induction of experimental autoimmune encephalomyelitis in Lewis rats by a viral peptide with limited homology to myelin basic protein.
Viral infections are thought to play an important role in the pathogenesis of multiple sclerosis potentially through molecular mimicry, but direct evidence from humans and animal models remains inadequate. Based on the fact that amino acid homology has been found between viral and host encephalitogenic protein, we designed four viral peptides (peptides of HBV polymerase protein, large T protein of JC virus, EB virus DNA polymerase and alkaline exonuclease of Human herpesvirus 6) with limited homology to myelin basic protein and explored their clinical, immunological and histological characteristics in Lewis rats. The immunization with JC virus peptide induced slight clinical signs of EAE in Lewis rats. Immunological examination indicated that rats immunized with JC virus peptide triggered T-cell cross-reactivity against MBP68-86, but failed to induce antibody cross-reactivity with MBP68-86. Histological staining exhibited the infiltration of inflammatory T cells and the activation of microglia in spinal cords of rats immunized with MBP68-86 and JC virus peptide. Other three peptides had negative findings in Lewis rats. These results suggested that molecular mimicry could be an important factor in the pathogenesis of EAE induced with JC virus peptide by expanding a population of reactive T cells that recognize MBP68-86 in Lewis rats inferring a possible pathogenesis for molecular mimicry in MS.
Mao
Yue-Shi
YS
Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 200040, Shanghai, China.
Lu
Chuan-Zhen
CZ
Wang
Xin
X
Xiao
Bao-Guo
BG
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000821:virology; D005260:Female; D007577:JC Virus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D004676:Myelin Basic Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D009187:Myelitis / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D004676:Myelin Basic Protein; D010455:Peptides; D014764:Viral Proteins