Identification of factors contributing to epigenetic alteration and maintenance in EBV infection.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chiba University
• Principal Investigator: Matsusaka Keisuke 千葉大学, 大学院医学研究院, 講師 (40610150)
• Research Collaborator: FUKUYO Masaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: DNAメチル化 / Epstein-Barr virus / 胃癌

Outline of Final Research Achievements

We demonstrated that Epstein-Barr virus (EBV) infection induced de novo DNA methylation in immortalized normal gastric epithelial cell, GES1, as well as gastric cancer cell, MKN7. Post-infection time-series DNA methylation analyses showed that EBV infection exerted strong pressure to induce de novo DNA methylation in gastric epithelial cells within a month in a spatiotemporally well-ordered manner. RNA-seq analysis showed that multiple EBV genes expression in early infection phase, indicating that complicated mechanisms should be involved in de novo DNA methylation induction. We established effective EBV dropout system using mutant EBNA1 labeled by fluorescent protein.

Free Research Field

エピジェネティクス、病理学

Academic Significance and Societal Importance of the Research Achievements

EBV関連腫瘍は、高齢化社会や高度先進医療に伴った免疫抑制状態で今後増加することが予想され、その対策は喫緊の課題である。本研究によりEBV感染がEBV陽性胃癌の際だったエピゲノム異常の原因であることが示され、その発がん機構にエピゲノム異常が重要であることが示された。また、EBV感染を効率的に脱落させられる系が確立し、EBVと宿主との相互作用に影響を及ぼす新規治療戦略の可能性が示された。