Polyomavirus Models of Brain Infection and the Pathogenesis of Multiple Sclerosis

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.