LncRNA NKILA在HIV病毒复制中的调控作用及机制研究

NF-kB信号通路在HIV病毒复制及潜伏性HIV病毒的重激活复制中扮演着重要的角色，靶向抑制NF-kB激活可能是具有前景的HIV-1治疗策略。近年来，一种结合NF-kB的长链非编码RNA NKILA被鉴定能够抑制人类多种癌症发展，其作用机制是通过抑制IKK诱导的IkB磷酸化及NF-kB信号的激活，但关于LncRNA NKILA对HIV病毒的调控作用未见报道。本项目目标是研究LncRNA NKILA与HIV复制的关系。前期结果显示它能够抑制HIV病毒的复制，抑制在HIV潜伏细胞模型中重新激活的HIV病毒复制，以及抑制HIV-LTR活性，这些结果显示它作为宿主抑制因子是通过调控HIV-LTR诱导的转录起始调控病毒的复制，并且这种抑制作用可能与其调控NF-kB活性的作用密切相关。本项目将深入揭示LncRNA对HIV病毒复制的调控机制，为抗HIV病毒的治疗药物研发提供新的靶点。

NF-kB pathway plays a key role in HIV replication and latency HIV viral reactivation. A regulator inhibiting NF-kB activation may be a promising therapeutic strategy against HIV-1. Recently an NF-KappaB Interacting LncRNA (NKILA) was identifed to suppress the development of different human cancers，by which that inhibited IKK-induced IkB phosphorylation and NF-kB pathway activation,but the relationship between LncRNA NKILA and HIV virus is still unknown. Therefore, in the present study, our results showed that LncRNA NKILA can inhibite HIV-1 replication and LTR activity, which indicated LncRNA NKILA as a host-intrinsic inhibitor, may interrupt the HIV-1 LTR-driven transcripitial initiation by decreasing NF-kB activation. This project will firstly introduce the relationship and mechanism of LncRNA NKILA with virus and represent a target for novel anti-HIV drug development.