Super-enhancer analysis of EBV-associated T/NK lymphoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15448
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Nagoya University
• Principal Investigator: Sato Yoshitaka 名古屋大学, 医学系研究科, 准教授 (40754940)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: Epstein-Barrウイルス / ゲノム高次構造 / ウイルス遺伝子発現

Outline of Final Research Achievements

Epstein-Barr virus (EBV) persists in human cells as episomes. EBV episomes are chromatinized and their 3D conformation varies greatly in cells expressing different latency genes. we compared the EBV episome intragenomic interactions in different cancer cell lines expressing three different types of EBV latency genes using a new method, HiChIP. H3K27ac HiChIPs were done in 4 T/NK lymphoma cell lines and 2 primary effusion lymphoma cell lines, together with published data from cell line expressing type III latency genes. We found that in type II latency infected cells, the episome looping patterns were similar to cells expressing type III latency genes. Similar to previous reports using a different method to compare the EBV 3D genome looping using captured Hi-C, more restricted type I latency infected cells had much less loopings. These data suggested that looping is a way for EBV to regulate its oncogene expression in various EBV associated cancer cells.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

ヒト腫瘍ウイルス Epstein-Barrウイルス（EBV）が陽性であるT/NK細胞性腫瘍（EBV関連T/NK細胞腫瘍）は日本をはじめとした東アジアで報告が多く、予後不良で有効な治療法は未だ存在しない。本研究では、ウイルスゲノムが感染細胞内で高次構造をとり、ウイルスゲノム内でのゲノム間相互作用の構造の違いにより、ウイルス遺伝子発現が制御されていることが明らかとなった。ゲノム編集によりEBVゲノムに構造変化を加えると、EBV遺伝子発現も変化し、ゲノム高次構造が治療標的となる可能性が示唆された。