High expression of polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy and nephropathy

Replication of JC virus (JCV) is associated with the pathogenesis of progressive multifocal leukoencephalopathy (PML). JCV encodes microRNA (miRNA) in its genome encoding large T antigen. JCV-encoded miRNA has been detected in the serum and cerebrospinal fluid samples of patients with and without PML. In the present study, we demonstrated high expression of JCV miRNA (miR-J1) in PML tissue samples with in situ hybridization. miR-J1 was detected in the nuclei of JCV-infected cells. In situ hybridization also demonstrated the expression of BK virus-encoded miRNA in the lesion of BKV-associated nephropathy. Higher copy numbers of miR-J1 were detected in PML tissues than non-PML tissues by real-time PCR. Next generation sequencing showed the 5p-miRNAs were predominant in the lesions. Mutant virus with deletion or mutant on miR-J1 resulted in progression of JCV replication, suggesting the suppressive role in the replication of JCV. These results indicated that polyomavirus-encoded miRNA as a possible candidate for depress the virus replication.