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Polyomavirus models of brain infection and the pathogenesis of multiple sclerosis
1Laboratory of Experimental Neuropathology, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Abstract:
Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with myelin as the target and with several unidentified viruses playing ancillary roles, possibly through molecular mimicry. Although this paradigm has led to important progress on potential mechanisms of myelin loss, neither a target antigen in myelin nor a triggering mechanism has yet been identified, leaving the etiology of MS still unknown. Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. A host immune response targeting proteins expressed at low levels from viral DNA latent in the central nervous system (CNS) might underlie a focal demyelinating disease such as MS. A shift from autoimmunity to a latent-virus model is not a trivial substitution of target antigens. This shift would expand the search for a definitive laboratory test for MS and could lead to improved therapeutic and preventive approaches.
Insights
Multiple sclerosis (MS) may stem from immune responses to latent viruses in the central nervous system (CNS), not just autoimmunity. This viral etiology could offer new diagnostic and therapeutic avenues for MS.
Area of Science:
- Neuroimmunology
- Virology
- Neurology
Background:
- Multiple sclerosis (MS) is typically viewed as an autoimmune disorder targeting myelin.
- Current understanding lacks identified myelin antigens or triggers, leaving MS etiology unknown.
- Viral triggers have been hypothesized via molecular mimicry but remain unproven.
Purpose of the Study:
- To propose an alternative etiological model for MS based on latent viruses.
- To explore the potential role of host immune responses to latent viral DNA in the CNS.
- To suggest how this model could impact MS diagnosis and treatment.
Main Methods:
- Review of existing literature on MS pathogenesis.
- Consideration of animal models of viral demyelination.
- Analysis of studies on JC virus (JCV) latency in the human brain.
Main Results:
- The traditional autoimmune model for MS has not identified specific targets or triggers.
- JC virus (JCV), a polyomavirus, can remain latent in the CNS.
- A latent-virus model suggests immune responses to low-level viral proteins could cause demyelination.
Conclusions:
- A shift from autoimmunity to a latent-virus model offers a new perspective on MS etiology.
- This model expands the search for diagnostic markers and potential therapies for MS.
- Investigating latent viral infections in the CNS may be crucial for understanding and treating MS.