Genomic instability of HTLV-1 provirus and application to clinical testing for adult T-cell leukaemia.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07670
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Kuramitsu Madoka 国立感染症研究所, 次世代生物学的製剤研究センター, 室長 (00566383)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HTLV-1 / genomic deletion / provirus / digital PCR / Adult T-cell Leukemia

Outline of Final Research Achievements

Deletion of the HTLV-1 proviral genome is known to occur at a high rate in adult T-cell leukaemia (ATL). In order to apply the detection of deletion of the proviral genome to clinical testing, the development of a quantitative assay was investigated.
Three sets of HTLV-1-specific primer-probes were designed and multiplexed (3-plex) by digital PCR to measure the relative ratio of HTLV-1 gene regions. The results of the examination of clinical specimens showed that deletions with a difference of more than 20% in the pX region could be detected at a viral load of more than 1.0%. Deletions were also detected in an extremely high proportion of some ATLs. This study shows that digital PCR can quantitatively and sensitively detect HTLV-1 provirus deletions.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

成人T細胞白血病（ATL）では、高頻度にHTLV-1ゲノムの欠失があることが知られ、また欠失型のプロウイルスを有するATLでは、完全型と比べて治療成績が異なることが報告されたことから、臨床検査でATL発症者のプロウイルスの欠失を簡便かつ鋭敏に捉えることは、治療戦略の策定にも役立ち重要と考えられる。本研究で開発したデジタルPCR法で、一部のATLでは欠失型プロウイルスが極めて高い割合を占めることを示ことが出来、プロウイルス欠失を定量的かつ高感度に検出できることを示した。臨床検査への応用が可能であることが確認された意義は大きいと考えられる。