Re-evaluation of a case of progressive multifocal leukoencephalopathy previously diagnosed as simian virus 40 (SV40) etiology.

A case of progressive multifocal leukoencephalopathy (PML) reported previously to be of simian virus (SV40) etiology was re-evaluated. The supernatant from a 10% homogenate of brain material was inoculated into African green monkey kidney cells and BSC-1 cells which are permissive for SV40. However no cytopathic effect (CPE) developed and no virus was isolated. The brain supernatant agglutinated human group O erythrocytes and contained 5120 units/mL. The Hirt supernatant from the brain contained three DNA bands corresponding to forms I, II and III of circular double-stranded viral DNA. Restriction endonuclease cleavage analysis revealed that this viral DNA was different from SV40 DNA, but similar to JC virus DNA. After cloning of this viral DNA into pBR322 at the BamHI site, DNA homology of this virus and of SV40 was investigated. Cloned DNA from the brain hybridized with all the HpaI/EcoRI fragments of the SV40 genome at the effective temperature of Tm -50 degrees C [corrected]. At Tm -28 degrees C, however, the cloned DNA hybridized with only HpaI/EcoRI fragment B of the SV40 genome. In contrast to this, JC virus DNA hybridized with all five EcoRI/BamHI/HindIII fragments of cloned DNA even at Tm -28 degrees C. Therefore, the causative agent of this PML case was not SV40 but JC virus.