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Viruses can silently prime for and trigger central nervous system autoimmune disease
D J Theil1, I Tsunoda, F Rodriguez
1Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Abstract:
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.
Insights
Viral infections can prime the central nervous system (CNS) for autoimmune disease. A subsequent, unrelated infection can trigger a relapse, offering insights into multiple sclerosis (MS) exacerbations.
Area of Science:
- Neuroimmunology
- Virology
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) pathogenesis remains unclear, though viral infections are linked to exacerbations.
- No single virus has been definitively identified as the cause of MS.
- Epidemiological data suggest a correlation between viral infections and MS flare-ups.
Purpose of the Study:
- To investigate if viral infections can "prime" the central nervous system (CNS) for autoimmune disease.
- To determine if a subsequent, non-specific challenge can trigger CNS autoimmune disease after initial viral priming.
- To explore potential mechanisms underlying MS exacerbations linked to viral infections.
Main Methods:
- Animals were infected with viruses exhibiting molecular mimicry with CNS antigens (GFAP, MAG, PLP).
- After the initial infection was cleared, animals received a non-specific challenge (e.g., CFA or irrelevant vaccinia virus).
- CNS tissues were analyzed for inflammatory cell infiltration and demyelination.
Main Results:
- Virus infections subclinically primed animals for CNS autoimmune disease.
- A non-specific challenge triggered exacerbations long after the initial viral infection.
- Mononuclear cell infiltration was observed in the CNS, but demyelination was absent.
Conclusions:
- Viral infections can establish a "primed" state in the CNS, predisposing it to autoimmune responses.
- Subsequent, unrelated infections or challenges can trigger CNS autoimmune disease exacerbations.
- This animal model may elucidate the mechanisms behind MS relapses associated with diverse viral infections.