Elucidation of the correlation between the structure of the membrane protein LMP1 derived from EB virus and its function of latent infection

2016 Fiscal Year Final Research Report

• Project/Area Number: 25282230
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Osaka University
• Principal Investigator: Inoue Tsuyoshi 大阪大学, 工学(系)研究科(研究院), 教授 (20263204)
• Co-Investigator(Kenkyū-buntansha): 安居 輝人 大阪大学, 微生物病研究所, 准教授 (60283074)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: Epstein-Barr（EB）ウイルス / 潜伏感染 / 不死化機構 / LMP1 / LMP2A / 膜蛋白質 / 自己免疫疾患 / リンパ腫

Outline of Final Research Achievements

Mice expressing membrane proteins LMP1 and LMP2A derived from EV virus were prepared and their effects were investigated. It was found that LMP2A promotes the differentiation of germinal center B cells into antibody producing cells and contributes to infection of EBV by surviving low affinity B cells. In addition, systemic lupus erythematosus-like symptoms were induced and firstly proved to be associated with autoimmune diseases.In addition, T / NK cells were reduced by using its antibody, and the pathological condition of the mouse was analyzed in the state of immunosuppression. It was found that LMP1 and LMP2A cooperate with each other in germinal center B cells and induce proliferative diseases such as Hodgkin's lymphoma.
The crystallization of the C-terminus region of CTAR1 involved in signal transduction in LMP1 was performed. The complex crystals between CTAR1 and its antibody of 11A1 up to 1.9 A resolution were obtained and the structural analysis is now in progress.

Free Research Field

構造生物学、基礎医学、免疫学