Mechanism of tumorigenesis in bovine leukemia initiated by chimeric transcripts of BLV-host genes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15005
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Hokkaido University
• Principal Investigator: Okagawa Tomohiro 北海道大学, 獣医学研究院, 特任助教 (80829036)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 牛伝染性リンパ腫 / BLV / キメラ転写産物 / ドライバー遺伝子 / 腫瘍化機序

Outline of Final Research Achievements

Enzootic bovine leukosis (EBL) is caused by infection with bovine leukemia virus (BLV), but the tumorigenesis mechanism of EBL remains unclear. Recently, it was hypothesized that antisense transcription is activated in EBL tumor cells initiated from the BLV provirus and that chimeric transcripts of BLV and its upstream driver genes contribute to tumorigenesis. In this study, a comprehensive analysis of provirus integration sites in EBL tumor cells were performed to identify driver genes located upstream of the provirus insertion sites in tumor cells. Furthermore, chimeric transcripts of BLV and specific driver genes were identified and their expression and ability to regulate the expression of downstream genes were analyzed.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

日本国内の農場では乳牛の41%、肉牛の29%がBLVに感染しており、この感染拡大に伴ってEBLの発生も国内で急増している。しかし、BLVの感染伝播や診断法に関する研究は盛んに進められている一方、BLVによるEBL発症機序に関する研究は限られている。本研究で得られた知見が、EBL発症リスクマーカーによる臨床診断やBLV感染牛の早期予後診断へと応用されれば、本疾病の制御による畜産被害の軽減につながると期待される。