Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS

JCV infects oligodendrocytes and, to a lesser extent, astrocytes in the brain and spinal cord and causes the demyelinating disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. The possibility exists that this opportunistic infection reactivates from a latent state in the brain. It is proposed that the pathogenetic immune response in a multiple sclerosis (MS) brain may be directed predominantly toward antigens of a DNA virus, such as JCV, which is latent in glial cells. The target antigens could be synthesized only during transient viral reactivation or could persist, thus explaining the two basic patterns of neurological symptoms in MS. It is further proposed that the viral genome as a minichromosome becomes focally distributed in glial cells following vertical passage in dividing progenitor cells after infection early in life. The concept that the host response to a single agent can evoke two distinct pathologies (PML and MS) derives from a chronic mycobacterial infection of peripheral nerves-leprosy.