Regulation of abortive lytic infection by EBV tegument proteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Fujita Health University
• Principal Investigator: Takayuki Murata 藤田医科大学, 医学部, 教授 (30470165)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: EBV / abortive lytic / tegument

Outline of Final Research Achievements

Recently, "abortive lytic" state of Epstein-Barr virus （EBV） has been focused by researchers, but its contribution to the infection and immortalization remains elusive. We here focused on the contribution of viral tegument proteins to the abortive lytic infection. Overall, we made a smooth progress and published some papers. Especially, RNAseq analyses of primary B cells infected with EBV provided many important data, although contribution of tegument proteins to abortive lytic cycle transcriptome appeared not as potent as we first expected when we started this project. For example, we found that EBV evades host immune reaction by over-expressing PD-L1 gene (Yanagi et al., Virology 2021). This induction of PD-L1 was predominantly achieved by viral latent protein EBNA2, but not viral tegument proteins. PD-L1 was increased by viral lytic cycle, but this was also brought about by EBNA2 but not tegument proteins (Yanagi et al. Virology 2022).

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

効率のよい感染の成立やがん化に重要であると考えられるが、その分子機構の大部分が未解明であったEpstein-Barr virus（EBV）の不完全溶解感染（abortive lytic)という状態について、新しい知見を得ることができた。このことはウイルス学、ひいては科学における学術的進展である。
また、EBVは感染直後主にEBNA2を介してPD-L1の発言を増強し、宿主免疫から逃避していることが明らかになった。すなわち、EBNA2を標的とした抗がん剤創薬が可能であること、さらにPD-1/PD-L1免疫チェックポイント阻害剤がEBVによるB細胞がん化を抑制できる可能性を示唆した。