Viruses can silently prime for and trigger central nervous system autoimmune disease.
Although many viruses have been isolated from patients with multiple sclerosis (MS), as yet, no one agent has been demonstrated to cause MS. In contrast, epidemiological data indicate that viral infections are associated with exacerbations of MS. Here, we present data showing that virus infections can subclinically prime animals for central nervous system (CNS) autoimmune disease; long after the original infection has been eradicated, a nonspecific challenge/infection can trigger an exacerbation. The priming infectious agent must show molecular mimicry with self-CNS antigens such as glial fibrillary acidic protein (GFAP), myelin associated glycoprotein (MAG) or myelin proteolipid protein (PLP). The subsequent challenge, however, may be nonspecific; complete Freund's adjuvant (CFA), or infection with a recombinant vaccinia virus encoding an irrelevant protein, could trigger CNS disease. In the CNS, we could detect a mononuclear cell infiltration, but no demyelination was found. However, if the pathogenesis of MS is similar to that of this novel animal model for CNS autoimmune disease, our findings could help explain why exacerbations of MS are often associated with a variety of different viral infections.
Theil
D J
DJ
Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Tsunoda
I
I
Rodriguez
F
F
Whitton
J L
JL
Fujinami
R S
RS
D000818:Animals; D002455:Cell Division / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005260:Female; D008214:Lymphocytes / Q000166:cytology / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000821:virology; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology; D014615:Vaccinia / Q000276:immunology* / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D018991:Myelin Proteolipid Protein; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins