Role of viral miRNA on tumorigenesis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22560
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Nagoya University
• Principal Investigator: Kimura Hiroshi 名古屋大学, 医学系研究科, 教授 (30303621)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: EBウイルス / miRNA

Outline of Final Research Achievements

Recently, we have found that there is a high rate of deletion of part of the EBV gene in patients with EBV-related lymphoma. Attempts were made to generate recombinant EBVs lacking the region containing the most frequently deleted viral miRNAs, but none of the produced viruses were infectious and did not lead to infection experiments. Next, a mutant EBV lacking BALF5 (viral DNA polymerase), which was the second most concentrated deletion, was created, and the established human B cell line was transplanted into immunodeficient mice. Lymphoma forming ability with BALF5-deleted EBV was increased in comparison with the wild-type strain. In addition, the BALF5-deficient B cell line had enhanced immediate-early / early genes as compared with the wild-type strain.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

期間内にmiRNA欠失の果たす役割の解明は果たせなかったが、欠損ウイルスでは、EBV前初期遺伝子/初期遺伝子の発現亢進により、宿主細胞増殖と染色体不安定性が促進され、ドライバー遺伝子変異の蓄積、エピジェネッティック修飾が加わり、リンパ腫/白血病と変容すると考えている。欠損ウイルスの腫瘍化機構が明らかになれば、EBV関連リンパ腫のみならず上咽頭がん・胃がんなどEBV関連上皮系腫瘍に共通する分子機構、さらには他の腫瘍ウイルスの発がんメカニズムが解明できる可能性がある。