Alteration in the JC polyomavirus genome is enhanced in immunosuppressed renal transplant patients

JC polyomavirus (JCV) DNAs derived from urine generally contain an archetypal regulatory sequence, whereas regulatory regions of JCVs in the brain with progressive multifocal leukoencephalopathy (PML) have specifically altered regulatory regions. However, JCV DNAs with regulatory regions that deviate from the archetype sometimes occur in the urine of non-PML patients. In this study, we compared the incidence of these rearranged regulatory regions between immunosuppressed (renal transplant recipients) and nonimmunosuppressed patients. We found that the incidence of rearranged JCV regulatory regions was significantly higher in renal transplant patients than that in nonimmunosuppressed patients. This finding suggests that immunosuppression would permit accumulation of JCV with rearranged regulatory regions. On the other hand, from the following observations, we conclude that rearranged regulatory regions unique to PML-type JCVs rarely occur even in renal transplant patients: (1) rearrangements in JCVs from these patients were almost exclusively simple, that is deletions or duplications; (2) duplication of domain A or deletion of domain B, each being a feature common to most PML-type regulatory regions, was rarely detected in JCVs from the patients. The data are consistent with the fact that PML is a rare disease in patients with decreased immune competence and support the hypothesis that changes in the JCV regulatory region may be involved with the etiology of PML.