Epigenetics analysis of HTLV-1 provirus through international comparison(Fostering Joint International Research)

2018 Fiscal Year Final Research Report

• Project/Area Number: 16KK0206
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kumamoto University
• Principal Investigator: Katsuya Hiroo 熊本大学, エイズ学研究センター, 特任助教 (80632041)
• Research Collaborator: Satou Yorifumi 熊本大学, エイズ学研究センター, 教授 ; Bangham Charles インペリアル大学, 医学部免疫学講座, 教授
• Project Period (FY): 2016 – 2018
• Keywords: HTLV-1 / 成人T細胞白血病・リンパ腫 / レトロウイルス / 転写制御

Outline of Final Research Achievements

We have developed the use of DNA probes for the capture of HTLV-1 fragments from a library prepared for next-generation sequence to efficiently analyze epigenetic features of the provirus. Using this approach, we found the novel enhancer region near the 3’LTR in HTLV-1. This enhancer region might contribute to keep HBZ expression constant, and thus maintain persistent HTLV-1 infection. DNA-capture-seq, furthermore, revealed that infected clones with defective-type provirus exhibited higher degree of clonal abundance than those with full-length type. This finding indicated that defective proviruses, which could not produce viral antigens, should allow the infected cell to escape from the host immune surveillance, resulting in clonal expansion of the infected cells.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

HTLV-1の新たな転写制御メカニズムを見出した。ウイルス遺伝子であるHBZの恒常的発現の機序の一つである可能性がある。HBZはHTL-1感染細胞の増殖に関わることが知られており、今後のHTLV-1感染細胞の増殖制御に関わる研究につなげることができる。