Studies on the mechanism of viral reservoir establishment based on crosstalk between HIV replication and immunometabolism.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07055
• 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: Kumamoto University
• Principal Investigator: Kishimoto Naoki 熊本大学, 大学院生命科学研究部附属グローバル天然物科学研究センター, 助教 (80756148)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HIV / 宿主因子 / 代謝 / 糖代謝リプログラミング

Outline of Final Research Achievements

The immune cells targeted by HIV show diverse metabolic states. Therefore, it becomes possible to discover new mechanisms for modifying HIV replication by tracking the factors undergoing functional changes due to metabolic shifts in immune cells. This approach may lead to elucidating the dynamics of HIV reservoir cells, which are the main obstacles to curing HIV infection. In this study, cells with different metabolic states were utilized to investigate HIV transmission and replication, identifying proteins that regulate HIV replication through post-translational modifications. This study found that HIV hijacks metabolic changes that are essential for immune cell activation, and proposed that glycolysis-related factors as endogenous factors that influence HIV transmission and dissemination.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

現在までのHIV研究の多くは、HIV複製効率を検証しやすくするために、高いウイルス産生能を有する細胞や高いHIV感受性を示す細胞、つまりHIVが複製しやすい環境に馴化された代謝シフトが完了した細胞」利用しており、HIV感染時に生体内で実際に起こる生理的に重要な免疫細胞の代謝シフトは十分には考慮されていない。一方本研究は、免疫代謝をウイルスがハイジャックした一端を捉えたものである。したがって、生体内での免疫細胞の代謝変動とともにHIV感染伝播の研究を進めることが新たな抗HIV治療戦略の構築に繋がることを示唆する。