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Updated: Dec 23, 2025

Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
Published on: July 13, 2019
High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its
Kenta Takahashi1, Yuko Sato1, Tsuyoshi Sekizuka2
1Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
Abstract:
JC polyomavirus (JCPyV, JCV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised hosts. JCPyV replicates in oligodendrocytes within the brain tissue of patients with PML. The JCPyV genome encodes a microRNA (miRNA) in the region encoding the large T antigen. JCPyV-encoded miRNA (miR-J1) has been detected in the tissue and cerebrospinal fluid samples of patients with PML; however, there are no reports describing the localization of polyomavirus-encoded miRNA in histological samples of patients with virus-associated diseases. In the present study, we detected high miR-J1 expression in the nuclei of JCPyV-infected cells in PML tissue samples via in situ hybridization. Additionally, in situ hybridization also revealed the expression of BK polyomavirus (BKPyV, BKV)-encoded miRNA in lesions of BKPyV-associated nephropathy. In situ hybridization for miR-J1-5p and -3p showed positive signals in 24/25 (96%) of PML tissues that were positive for JCPyV by immunohistochemistry. Higher copy numbers of miR-J1 were detected in PML tissues than in non-PML tissues by real-time reverse transcription PCR. Next generation sequencing showed that miR-J1-5p, a mature miRNA of primary miRNA, was predominant in the lesions compared with miR-J1-3p, another mature miRNA. Deletion or mutation of miR-J1 in recombinant JCPyV promoted the production of JCPyV-encoded proteins in cells transfected with JCPyV DNA, suggesting that polyomavirus-encoded miRNA may have a repressive role in viral replication in PML tissues. In situ hybridization for viral miRNA may be a useful diagnostic tool for PML.
Insights
JC polyomavirus (JCPyV) microRNA (miR-J1) is highly expressed in the nuclei of infected cells in progressive multifocal leukoencephalopathy (PML) tissue. This viral miRNA may repress JCPyV replication, suggesting its diagnostic potential for PML.
Area of Science:
- Virology
- Molecular Biology
- Pathology
Background:
- JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals.
- JCPyV encodes a microRNA (miRNA), miR-J1, within its genome.
- Localization of viral miRNAs in pathological tissues has not been previously reported.
Purpose of the Study:
- To investigate the localization and potential role of JCPyV-encoded miRNA (miR-J1) in PML.
- To explore the diagnostic utility of in situ hybridization for viral miRNAs in PML.
Main Methods:
- In situ hybridization was used to detect miR-J1 expression in PML tissue samples.
- Immunohistochemistry confirmed JCPyV presence.
- Real-time reverse transcription PCR and next-generation sequencing quantified miR-J1 levels.
- Recombinant JCPyV with deleted/mutated miR-J1 was used to assess its role in viral protein production.
Main Results:
- High miR-J1 expression was detected in the nuclei of JCPyV-infected cells in PML tissues.
- miR-J1 was also detected in BK polyomavirus-associated nephropathy lesions.
- miR-J1 was significantly more abundant in PML tissues than non-PML tissues.
- Deletion of miR-J1 in recombinant JCPyV increased viral protein production, suggesting a repressive role.
Conclusions:
- Viral miRNAs, such as miR-J1, are localized within infected cells in virus-associated diseases.
- miR-J1 may play a regulatory role in JCPyV replication.
- In situ hybridization for viral miRNAs could be a valuable diagnostic tool for PML.
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