HIV-1潜伏不能被药物根除是当前AIDS治疗的难点之一。抑制HIV-LTR驱动的前病毒DNA的转录是HIV-1维持潜伏的关键。宿主因素参与前病毒DNA转录调控；抑制性染色质构象是HIV-1转录抑制的关键因素。宿主蛋白Sun2可与核纤层蛋白（Lamin A/C）作用，维持抑制性染色质。前期工作提示：1）Sun2抑制LTR驱动的转录和病毒复制;2)干涉Sun2增强HIV-1潜伏激活；3）HIV-1潜伏激活减弱Sun2与Lamin A/C的作用。因此提出假说，Sun2与Lamin A/C作用，维持抑制性染色质，阻止转录因子招募至LTR，抑制病毒转录，维持HIV-1潜伏。从以下证明假设：1）阐明Sun2-Lamin A/C相互作用对维持HIV-1潜伏和抑制复制的重要性；2）利用HIV-1潜伏模型，探究Sun2通过维持异染色质调控病毒潜伏的分子机制。期望通过揭示HIV潜伏机制，探讨潜伏治疗新策略。

HIV-1 reservoir due to viral latency that cannot be eradicated by antiretroviral therapy represents one of the major obstacles for sterilizing. The silencing of HIV-1-LTR promoter-driven transcription is the critical mechanism for maintaining viral latency. The transcription of HIV-1 proviral DNA can be modulated by host factors, amongst the repressive chromosome or heterochromatin structure is the key for transcriptional silencing. It has been reported that the host protein Sun2 interacting with Lamin maintains the repressive chromosome. Our preliminary studies suggest; 1) Sun2 suppresses HIV-1-LTR-driven transcription; 2) Sun2 maintains HIV-1 latency, as the interference of Sun2 expression promotes HIV-1 reactivation from latency; 3) The HIV-1 reactivation from latency attenuates the interaction of Sun2-Lamin interactions. Therefore, we proposed to delineate the mechanism of Sun2 regulating HIV-1 latency. Our central hypotheses are: the interplay of Sun2-Lamin maintains the repressive chromosome, and blocks the recruitment of host transcriptional factors to HIV-1 LTR-promoter, therefore, HIV-1 transcription is suppressed and viral latency is maintained. We propose two specific aims to test these novel hypotheses: 1) To investigate the modulation of Sun2-Lamin interplay on HIV-1 latency； 2) To determine the mechanism of Sun2 maintaining the repressive chromatin to control latency in detail, using HIV-1 latently infected cells. Accomplishing the proposed studies will provide novel insights into the cellular mechanisms of modulating HIV-1 latency, and facilitate seeking for a new approach to overcome viral latency.