Analysis of the mechanisms for transient expression of HTLV-1 Tax and development of novel immunotherapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kyoto University
• Principal Investigator: Yasunaga Jun-ichirou 京都大学, ウイルス・再生医科学研究所, 講師 (40362404)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HTLV-1

Outline of Final Research Achievements

It was found that both transient expression of Tax and continuous expression of HBZ are important for the maintenance of ATL cell lines, such as MT-1 and KK-1. This finding was published PNAS (Mahgoub M, Yasunaga JI, Iwami S, Nakaoka S, Koizumi Y, Shimura K, and Matsuoka M. Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells. Proc Natl Acad Sci USA, 2018. doi: 10.1073/pnas.1715724115). ATAC-seq and ChIP-seq were carried out to see the effect of the transient expression of Tax on the epigenetic status of host cells. Analysis using HBZ transgenic mice showed that IL-10 plays important roles in T-cell proliferation induced by HBZ.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

Taxは強力ながん蛋白質であるが、免疫原性が高いためATL細胞では発現が抑制されており、発がんにおける意義は不明であった。本研究により、Taxの一過性発現とHBZの持続発現の発がんにおける意義を初めて報告した。本研究で得られた知見はHTLV-1の潜伏機構、発がん機構の解明に寄与できると考える。本研究で行ったTaxの発現誘導とTaxワクチンの併用療法の開発をさらに推進することで、ATLの発症予防法、再発予防法の開発に繋がると考える。