DNA结合/分化抑制因子2调控HIV-1潜伏感染活化过程的作用及机制研究

HIV病毒潜伏储存库的存在是导致艾滋病无法彻底治愈的主要原因。阐明HIV-1潜伏储存库形成以及活化的分子机制，探索新的艾滋病治愈策略，已成为艾滋病研究领域的重心。申请人前期研究发现DNA结合/分化抑制因子2（Id2）能负性调控HIV-1转录及潜伏活化过程，且该作用与细胞周期调控以及SAMHD1密切相关。因此，本项目拟深入揭示Id2在HIV-1潜伏感染活化过程中的关键调控作用，并阐明Id2/CDK2/SAMHD1调控HIV-1潜伏活化的分子机制，探讨Id2作为HIV-1潜伏感染激活剂新靶点的可能性。主要研究内容包括：1）通过敲除以及过表达技术探明Id2在HIV-1潜伏感染活化过程中的作用；2）阐明Id2调控HIV-1潜伏感染活化过程的分子机制。本项目将进一步阐明HIV-1病毒潜伏储存库形成及活化的分子机制，为研发出新型HIV-1潜伏感染激活剂奠定理论基础，实现HIV-1“功能性治愈”的目的。

The persistence of HIV latent reservoirs is a major barrier to achieve a complete cure for AIDS.Elucidating the molecular mechanism of HIV-1 latent reservoir formation and activation and exploring new AIDS cure strategies have become the focus of AIDS research. The applicant's previous studies have found that DNA binding / differentiation inhibitor 2 (Id2) can negatively regulate HIV-1 transcription and latent activation, and this effect is closely related to cell cycle regulation and SAMHD1. Therefore, this project intends to further reveal the key regulatory role of Id2 in the process of HIV-1 latent infection activation, clarify the molecular mechanism of Id2 / CDK2 / SAMHD1 regulating HIV-1 latent activation, and explore the possibility of Id2 as a new target of HIV-1 latency reversing agents. The main research contents include: 1) to explore the role of Id2 in the activation process of HIV-1 latent infection by knockout and overexpression technology; 2) to clarify the molecular mechanism of Id2 regulating the activation process of HIV-1 latent infection. This project will further clarify the molecular mechanism of HIV-1 latent reservoir formation and activation, lay a theoretical foundation for the development of new HIV-1 latency reversing agents, and achieve the purpose of "functional cure" of HIV-1.