课题基金基金详情
三氧化二砷诱导HIV病毒储存库细胞凋亡的机制研究
结题报告
批准号:
32000124
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李平超
学科分类:
病毒学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李平超
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中文摘要
艾滋病毒(HIV)感染严重威胁全球公共卫生,有效清除潜伏感染的病毒储存库(latent viral reservoir,LVR)是根治艾滋病的关键。我们发现抗癌药物三氧化二砷(As2O3)在多种细胞模型中高效激活LVR,与抗逆转录病毒疗法(ART)联合可有效治疗猴艾滋病毒(SIV)慢性感染猕猴(Advanced Science,2019,IF=15.804)。但该药物影响LVR的作用机制尚未被阐明。As2O3治疗白血病的机制主要是诱导细胞凋亡,我们近期研究也表明As2O3能促进LVR细胞凋亡。在此基础上,本项目将利用多种LVR细胞模型和SIV感染的猕猴细胞模型,通过流式细胞术、病毒储存库检测技术、RNA-seq等技术研究As2O3对细胞凋亡通路的影响,系统分析As2O3诱导的细胞凋亡与病毒储存库激活的关系,以揭示As2O3影响LVR的分子作用机理,这将为艾滋病的功能性治愈提供理论依据。
英文摘要
HIV infection has become a serious threat to global public health, and effectively elimination of the latent viral reservoir (LVR) is the key to eradication of AIDS. We found that the cancer medicine, arsenic trioxide (As2O3), can efficiently reverse LVR in cell models, and it can effectively treat chronically simian immunodeficiency virus (SIV) infected rhesus macaques in combination with antiretroviral therapy (ART) (Advanced Science, 2019, IF = 15.804). However, the mechanism of the medicine's effect on LVR has not been elucidated. The mechanism of As2O3 treatment of leukemia is mainly to induce apoptosis. Our recent research also showed that As2O3 can induce apoptosis of LVR cells. On this basis, this project will use a series of LVR cell models and SIV-infected rhesus macaques cell models to study the effect of As2O3 on the apoptosis pathway through flow cytometry, viral reservoir detection technology, RNA-seq and other technologies. We will also analyze the relationship between As2O3-induced apoptosis and viral reservoir reversal to reveal the molecular mechanism of As2O3 affecting LVR. This will provide theoretical guidance for the functional cure of AIDS.
期刊论文列表
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科研奖励列表
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专利列表
DOI:10.1128/jvi.01785-21
发表时间:2022-02-01
期刊:JOURNAL OF VIROLOGY
影响因子:5.4
作者:Wu, Chunxiu;He, Yizi;Sun, Caijun
通讯作者:Sun, Caijun
DOI:10.1007/s12250-021-00407-6
发表时间:2021-10
期刊:Virologica Sinica
影响因子:5.5
作者:Wu C;Zhao J;Li R;Feng F;He Y;Li Y;Huang R;Li G;Yang H;Cheng G;Chen L;Ma F;Li P;Sun C
通讯作者:Sun C
DOI:10.1128/spectrum.00525-23
发表时间:2023-09-11
期刊:Microbiology spectrum
影响因子:3.7
作者:
通讯作者:
新型SMAC类似物APG-1387通过非经典NF-κB信号激活HIV潜伏储存库的机制研究
ICAM-1在流感病毒特异性CD8+ T细胞迁移到呼吸道中的作用研究
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海外基金