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.

Plos Pathogens
|April 24, 2020
PubMed

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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