Targeted inhibition of HIV-1 latency

人类免疫缺陷病毒1型（HIV）通过免疫细胞的长时间潜伏感染破坏被感染者的免疫系统。了解调节潜伏期的分子机制可能会导致针对抑制这一过程和清除HIV细胞储存库的策略。我们已经了解到HIV表达的反义长链非编码RNA （lncRNA）在表观遗传上调节病毒转录中的作用。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展我们目前对艾滋病毒感染的理解，并为调节病毒表达提供新的途径，这可能与清除病毒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.