Naturally occurring and passage-induced variation in the genome of JC virus

We have examined both the naturally occurring and passage-induced variation in the genome of the human polyomavirus, JCV. JCV DNA was extracted directly from diseased brain tissue of ten cases of progressive multifocal leukoencephalopathy (PML) and the DNA population from any one case was homogeneous with respect to length and restriction endonuclease cleavage patterns. However, a comparison of cloned JCV DNAs revealed that the viral DNAs derived from different cases of PML were not identical. We identified a hypervariable region near the origin of DNA replication, and we demonstrated that there are two genetically distinguishable subtypes of the virus. After growth in vitro, the DNA from certain isolates of JCV became heterogeneous in size. Deletions of up to 12% of the genome occurred after as few a three low multiplicity passages in human glial cells. Most of the deletions mapped within the region presumed to code for T antigen. In addition, we examined the physical properties of JCV from brain and, as expected, they were typical of the polyomavirus genus.