JC virus (JCV) causes a fatal demyelinating disease in AIDS patients known as progressive multifocal leukoencephalopathy (PML), and there is evidence that JC virus (JCV) establishes latency in the kidney in a significant part of the human population. This investigation was undertaken to study the possible role of latent JCV in human neurologic diseases of unknown etiology. The first diseases being studied are the demyelinating diseases, multiple sclerosis (MS) and a primitive neuroectodermal tumor (PNET) known as medulloblastoma. Using oligonucleotide primers specific for the regulatory region or the coding region genes (early and late), JCV DNA was amplified from brain tissues by the polymerase chain reaction (PCR). The data obtained indicate that JCV DNA is present in lO of 26 normal brains or other neurologic diseases, 4 of 5 multiple sclerosis and 4 of 5 medulloblastoma brain samples. Cloning and DNA sequence analysis of the regulatory region specific PCR-amplified products revealed that the tissues contained regulatory region sequences like the Mad-1 prototype isolated in Madison, Wisconsin in 1971. Amplifications using JCV archetype-specific primers were negative with all the tissues, suggesting that PML-type deletions and duplications have occurred in these neurotropic strains of JCV and arguing against contamination of specimens by urinary virus during handling (or by kidney-type virus contained within vessels in the brain tissues). While the role of JCV DNA sequences in the MS and medulloblastoma samples remains to be established, the data appear to confirm the existence of latency by JCV in the CNS. It is tempting to propose that MS, medulloblastoma and progressive multifocal leukoencephalopathy (PML) may represent different host responses to. the presence of latent JCV in the brain following infection early in life.
