Targeted inhibition of HIV-1 latency

描述（由申请人提供）：HIV-1潜伏期的靶向抑制概述1型人类免疫缺陷病毒（HIV）通过延长免疫细胞的潜伏感染来破坏感染个体的免疫系统。对调节潜伏期的分子机制的理解可能会导致旨在抑制这一过程和清除HIV细胞库的策略。我们已经了解到，HIV表达的反义长非编码RNA（lncRNA）在表观遗传学上调节病毒转录中起作用。在这个项目中，我们建议从机制上验证这种lncRNA在驱动病毒潜伏期中的作用，确定哪些宿主蛋白参与了这一过程，并开发一种创新的策略来治疗细胞，使病毒无法进入潜伏期。该项目的完成将大大扩大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表达，这可能证明与清除病毒储存库的治疗策略以及开发艾滋病毒疫苗的可能方法有关。

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.