Targeted inhibition of HIV-1 latency

描述(由申请人提供)：针对HIV-1潜伏期的抑制摘要人类免疫缺陷病毒1型(HIV)通过延长免疫细胞的潜伏感染来破坏感染者的免疫系统。对潜伏期调节分子机制的理解可能导致旨在抑制这一过程和清除细胞内艾滋病毒储存库的策略。我们已经了解到，HIV表达的反义长非编码RNA(LncRNA)在表观遗传中调节病毒转录。在这个项目中，我们建议从机械上验证这种lncRNA在驱动病毒潜伏期方面的作用，确定哪些宿主蛋白参与了这一过程，并开发出一种创新的策略来治疗细胞，使病毒无法进入潜伏期。该项目的完成将极大地扩展我们目前对艾滋病毒感染的理解，并提供新的途径来调节病毒的表达，这可能被证明与清除病毒库的治疗战略以及开发艾滋病毒疫苗的可能方法都相关。

DESCRIPTION (provided by applicant): Targeted inhibition of HIV-1 latency Summary Human Immunodeficiency Virus type 1 (HIV) ravages the immune system of infected individuals by prolonged latent infection of immune cells. An understanding of the molecular mechanisms regulating latency could lead to strategies aimed at either inhibiting this process and purging cellular reservoirs of HIV. We have learned that an HIV expressed antisense long non-coding RNA (lncRNA) functions in epigenetically modulating viral transcription. In this project we propose to mechanistically validate the role of this lncRNA in driving viral latency, determine what host proteins are involved in the process, and develop an innovative strategy to treat cells such that the virus cannot enter latency. The completion of this project will significantly expand our current understanding of HIV infection and provide new avenues to modulate viral expression that may prove relevant in both therapeutic strategies to purge viral reservoirs as well as possible approaches to develop an HIV vaccine.