Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice.
Semliki Forest Virus (SFV) induces an encephalomyelitis followed by demyelination in the brains of C57Bl6/J (B6) mice. To investigate the role of molecular mimicry in the pathogenesis of postviral demyelination, alignment algorithms were used and amino acid homologies between immunogenic epitopes of SFV and myelin autoantigens, myelin basic protein (MBP), myelin proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) were identified. Immunization of B6 mice with SFV proteins induced significant lymphocyte proliferation to SFV E2 peptides and to MOG peptide, 18-32 (which had molecular mimicry with E2 115-129), but not to MBP or PLP peptides. Both MOG 18-32 and E2 115-129, induced a later-onset chronic EAE-like disease that correlated with the presence of multifocal vacuolation in the CNS white matter. This histopathology was reminiscent of the secondary demyelination seen following SFV infection. Serum antibody responses to the peptides appeared late after immunizations and some samples cross-reacted with other myelin peptides, as well as with the mimicked MOG peptides. These findings suggest that following a CNS viral infection, antibody response to an epitope of virus that exhibits molecular mimicry with a peptide of MOG may contribute to autoimmune mediated injury to CNS myelin.
Mokhtarian
F
F
Department of Medicine, SUNY, Health Science Center and Maimonides Medical Center, Brooklyn, NY 11219, USA. drfmsuny@idt.net
Zhang
Z
Z
Shi
Y
Y
Gonzales
E
E
Sobel
R A
RA
D000208:Acute Disease; D018354:Alphavirus Infections / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002490:Central Nervous System / Q000737:chemistry / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D003429:Cross Reactions; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry* / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D012672:Semliki forest virus / Q000737:chemistry* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014764:Viral Proteins