HTLV-1长期潜伏于宿主细胞导致无症状携带者处于慢性持续感染阶段，始终是进展为高致死率的成人T细胞白血病(ATL)的危险因素。然而，病毒感染细胞如何能长期潜伏于具有免疫能力的宿主？目前尚未明确。近期研究表明，Sirt1对T淋巴细胞的激活具有负调节作用，而HIV病毒抑制Sirt1表达及功能是导致T细胞耗竭的原因之一。我们在前期对HTLV-1感染T细胞的Sirt1表达水平进行检测时发现病毒Tax与感染细胞Sirt1过表达存在关联，而且Sirt1的过表达有助于抵抗氧化应激诱导的细胞凋亡。本课题拟采用ChIP、免疫共沉淀、荧光素酶报告基因、CTL细胞毒性离体实验、感染动物模型等技术方法，从分子、细胞水平和动物模型系统地探讨Tax介导的Sirt1过表达是否是HTLV-1 感染细胞抵抗凋亡和宿主CTL反应的重要机制之一，从而为无症状HTLV-1病毒携带者的早期监控和适时干预提供可行的防治策略。

The long-term latency of human T-cell lymphotropic virus-1(HTLV-1) in host cells causes chronic persistent infection in asymptomatic HTLV-1 carriers, which is a risk factor for the high mortality rate of adult T-cell leukemia (ATL).However,it is still unclear how virus-infected cells could long-term existed in host with competent immune system. Recent studies have shown that Sirt1 played a negative regulatory role in the activation of T lymphocytes, and the inhibition of expression and fuction of Sirt1 in HIV was regarded as one of the reasons for T cell depletion. In our previous research, we found that there was an association between Tax and Sirt1 overexpression in HTLV-1 infected T cells, and overexpression of Sirt1 contributed to the resistance to oxidative stress-induced apoptosis in HTLV-1 infected T cells. This project will explore whether Tax-mediated Sirt1 overexpression is one of the important mechanisms of resistance to apoptosis and host cytotoxic lymphocyte (CTL) response in HTLV-1 infected cells in various levels (e.g. molecular level, cellular level and aninmal model system) by using chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation assay, luciferase reporter gene assay, CTL cytotoxicity assay ex vivo and in vivo HTLV-1 infection assay in an animal model, etc., and the clarification of this issue would provide a feasible prevention strategy for asymptomatic HTLV-1 virus carriers in early monitoring and timely intervention.