Origin of JC polyomavirus variants associated with progressive multifocal leukoencephalopathy

JC polyomavirus (JCV) DNAs from the urine of nonimmunocompromised individuals (designated archetypal isolates) regularly contain a regulatory sequence that may have generated various regulatory sequences of JCV isolates derived from the brain of patients with progressive multifocal leukoencephalopathy (PML). In this report, we constructed a phylogenetic tree for 14 isolates (7 archetypes and 7 PML types) from DNA sequence data on the VP1 (major capsid protein) gene. According to the phylogenetic tree, the 14 isolates diverged into types A and B, each of which contained archetypal and PML-type isolates. Each type further diverged into several groups containing archetypal and PML-type isolates. We conclude that PML-type isolates are polyphyletic in their origin and do not constitute a unique lineage. This conclusion suggests that PML-type JCV isolates are generated from archetypal strains during persistence in the hosts. Furthermore, the present phylogenetic analysis indicates that an ancestral JCV carried the archetypal regulatory sequence and that this structure has been conserved in the course of JCV evolution.