Pathological diagnosis targeting JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15174
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Takahashi Kenta 国立感染症研究所, 感染病理部, 主任研究官 (80711689)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 進行性多巣性白質脳症 / JCウイルス / マイクロRNA / In situ hybridization

Outline of Final Research Achievements

JC polyomavirus (JCV) is a causative agent of progressive multifocal leukoencephalopathy (PML). MicroRNAs (miRNAs) are short fragments of RNA with 20-22 mer length. Almost all animals encode miRNAs in their genomes and many DNA viruses also encode thier own miRNAs. Viral miRNAs bind to host mRNAs and affect their translation.
In this study, high expression and nuclear localization of polyomavirus-encoded miRNAs were demonstrated in tissues from PML cases by in situ hybridization. The sensitivity of in situ hybridization for viral miRNA was comparable to that of immunohistochemistry. Therefore, in situ hybridization targeting viral miRNA may be a useful diagnostic tool for PML. Additionally, the deletion of viral miRNA coding region in JCV DNA resulted in high expression of viral proteins in JCV DNA-transfected cells, implying an autoregulation mechanism in virus replication as well as the possibility that viral miRNA may be a new therapeutic tool for PML.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

本研究ではウイルス由来のマイクロRNAに着眼し、JCウイルス感染症である進行性多巣性白質脳症の実際の病理組織標本上で、ウイルス由来マイクロRNAの感染細胞における局在を世界で初めて明瞭に示した。また培養細胞を用いた実験系では、ウイルス由来マイクロRNAがウイルス自身の増殖に抑制的に作用していることを明らかにした。
ウイルス由来マイクロRNAを標的とした、感染症の新しい病理組織診断法や新規治療法の開発が期待される。