ISlncRNA-23促进HIV-1复制的机制研究

Interferon (IFN) is a key molecule in anti-HIV response, which mainly acts through IFN-stimulated genes. While the antiviral functions of proteins encoded by IFN-stimulated genes have been extensively studied, the functions of IFN-stimulated long noncoding RNAs (LncRNAs) remain largely unknown. In our previous studies, we performed lncRNA microarray analysis and isolated about 100 lncRNAs that are upregulated in response to type I IFN. ISlncRNA-23, a novel lncRNA, was found to be involved in the regulation of HIV-1 production. Overexpression of ISlncRNA-23 enhanced the production of VSV-G pseudotyped HIV-1 vector, and downregulation inhibited viral production. ISlncRNA-23 had little effect on Gag expression in the producer cells but significantly increased p24 levels in the culture supernatants, which indicates that it may affect HIV-1 assembly or budding. This project is aimed at better understanding of the mechanisms underlying ISlncRNA-23 enhancement of HIV-1 production. The results of this project is expected to broaden our understanding of the complex roles of IFN in regulating HIV-1 replication.

干扰素通过诱导抗病毒蛋白发挥抗HIV功能的研究已有许多报道，但关于干扰素诱导的长链非编码RNA（lncRNA）对HIV复制的影响鲜见报道。前期研究中，我们鉴定了100左右个受干扰素诱导表达上调的lncRNA，并筛选具有调控HIV复制功能的lncRNA，发现了一个未曾报道的lncRNA，ISlncRNA-23。过表达该lncRNA显著促进HIV-1的复制，敲低则抑制其复制。ISlncRNA-23不影响包装细胞中Gag的表达，但明显促进了上清病毒颗粒p24的量，表明其影响HIV-1的组装或出芽。本项目拟深入研究ISlncRNA-23调控HIV复制的分子机理。一方面，该研究有助于深入了解长链非编码RNA作用的分子机理；另一方面，本研究前期结果提示了干扰素诱导基因在调控HIV复制方面的复杂性，本研究有助于我们加深对这种复杂性的理解。