| 研究課題/領域番号 |
22K16374
|
|---|
| 研究種目 |
若手研究
|
| 配分区分 | 基金 |
|---|
| 審査区分 |
小区分54030:感染症内科学関連
|
|---|
| 研究機関 | 熊本大学 |
|---|
研究代表者 |
BARABONA GODFREY 熊本大学, ヒトレトロウイルス学共同研究センター, 特別研究員 (40906674)
|
|---|
| 研究期間 (年度) |
2022-04-01 – 2024-03-31
|
| 研究課題ステータス |
交付 (2022年度)
|
| 配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2023年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2022年度: 2,730千円 (直接経費: 2,100千円、間接経費: 630千円)
|
|---|
| キーワード | Extracellular vesicle / HIV / Inflammation / MicroRNA |
|---|
| 研究開始時の研究の概要 |
This study will analyze circulating microRNAs that are delivered by extracellular vesicles and determine their role in systemic immune dysfunction and chronic inflammation seen in HIV infection. The central hypothesis is that, in HIV infection, microRNAs are dysregulated and play a crucial role in the persistent immune dysfunction and chronic inflammation.
|
| 研究実績の概要 |
Our project had two main specific aims: (1) to identify circulating miRNAs that are altered in HIV-infected individuals, and (2) to investigate whether altered miRNAs in extracellular vesicles from HIV patients regulate cytokine expression ex vivo. Over the past year of project implementation, we have collected three sets of plasma samples: from HIV-infected individuals before and after treatment, and from HIV-uninfected individuals. Using these samples, we have demonstrated a differential relative expression of miRNAs in plasma extracellular vesicles (EVs). Notably, our preliminary data suggest a trend of downregulation of EV miRNAs in the untreated HIV-infected group compared to the treated and HIV-uninfected groups. Our extended analysis further indicates that absolute levels of miRNA are lower in HIV-infected untreated individuals compared to treated and uninfected individuals. Additionally, we found that plasma miRNAs were more abundant compared to miRNAs in EVs but followed a similar trend to that of EVs. Given that absolute levels of miRNAs seem to be low in most individuals, we intend to first demonstrate the effect of EV miRNAs from HIV-infected individuals compared to those from HIV-uninfected individuals in vivo.
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have successfully obtained the plasma samples required for our study and conducted our initial experiments and analysis. However, we have observed that the levels of miRNAs in EVs are generally low, which may limit their physiological significance. However, we acknowledge that this observation is limited to a small set of miRNAs investigated. Therefore, to further explore the potential impact of miRNAs in EVs on inflammation, we plan to investigate their effects on macrophage inflammation state in vivo. This will allow us to demonstrate the plausibility that miRNAs in EVs at physiological levels can influence inflammation.
|
| 今後の研究の推進方策 |
We intend to use monocyte-derived macrophages to investigate the impact of EV extracted from HIV-infected individuals and compared it to that from HIV-uninfected individuals. We will use cytokine expression levels to detect the impact of the EV content on the inflammation state. Following this series of experiments, we will then use the combination of next-generation sequencing and bioinformatics tools to identify potential microRNA responsible for the modulation of cytokines expressions in macrophages. To confirm the contribution of miRNA cargo in cytokine production, we will conduct another experiment in the presence of specific anti-miRNAs corresponding to the miRNA candidates that are altered in extracellular vesicles of HIV patients. Finally, we will confirm our observation by transfection of mimic miRNA for each miRNA whose expression in extracellular vesicles of HIV infected individuals were altered
|
