固有免疫应答通过诱导干扰素和干扰素调控基因的表达，有效抑制寨卡病毒的复制、传播与致病。我们前期发现：79个宿主长链非编码RNA（lncRNA）在寨卡病毒感染后差异性表达，其中部分lncRNA的诱导表达依赖于干扰素的产生。那么，这些差异表达的lncRNA是否对寨卡病毒的复制有影响？我们进一步证实：一个全新的lncRNA分子ZSR3可显著抑制寨卡病毒的复制，并正反馈调控干扰素的产生。我们推测ZSR3是一个新的干扰素调控基因，其表达受到干扰素的调控，并具有抗病毒功能。本项目拟探索寨卡病毒诱导ZSR3高表达的分子机制；分析ZSR3的生物学特性；确定其抗病毒的功能及作用阶段；重点阐明ZSR3正反馈调控干扰素产生的分子机制，验证ZSR3的抗病毒效应是否完全依赖于干扰素的产生。本项目研究成果将揭示固有免疫应答、lncRNA与寨卡病毒的相互关系，为lncRNA作为抗寨卡病毒药物的新靶点提供理论依据。

Innate immune response effectively control the replication, dissemination, and pathogenesis of Zika virus (ZIKV) through inducing the expression of interferons (IFNs) and downstream IFN-stimulated genes. Our preliminary data showed that the expression of 79 host long non-coding RNAs were altered by ZIKV infection, and the expression of some ZIKV-induced lncRNAs was dependent on innate immunity. Are the differentially-expressed lncRNAs involved in ZIKV replication? Our further study identified a novel lncRNA, ZSR3, significantly inhibited the ZIKV replication, and played a role in the production of IFNs induced by ZIKV. We proposed that ZSR3 is a novel interferon-stimulated gene, which expression is regulated by IFNs and confers an antiviral activity. Current study will explore the mechanism of ZSR3 expression induced by ZIKV infection and analyze the biological characteristics of ZSR3. We will confirm the antiviral role of ZSR3 and distinguish at what stage(s) it acts. Finally, we will illustrate the molecular mechanism of how ZSR3 promotes the production of IFNs, and validate that the antiviral effect of ZSR3 relies on its regulatory effect on the IFNs. Our study will shed light on the relationship among innate immune response, lncRNA, and ZIKV, providing evidence that lncRNAs are promising targets of anti-ZIKV drugs.