病毒感染可激活宿主的I型干扰素（IFN）应答，引起数以百计的干扰素刺激基因（ISGs）的转录，而ISGs可调控病毒复制的不同阶段。猪瘟（CSF）是由猪瘟病毒（CSFV）引起的一种严重危害养猪业的烈性传染病。此前我们证实，宿主细胞HB蛋白可通过激活IFN信号通路抑制CSFV的复制，但目前对ISGs的抗CSFV作用及其分子机制尚不清楚。本项目拟利用流式细胞术、荧光素酶报告病毒筛选抗CSFV ISGs；然后，通过siRNA下调表达和慢病毒介导过表达ISGs，用亲本病毒验证筛选的ISGs的抗病毒活性；之后，从ISGs与CSFV蛋白的相互作用、ISGs对IFN信号通路的调控以及抗病毒ISGs参与病毒复制周期的具体阶段等方面，揭示ISGs抗CSFV的分子机制；最后，通过检测其对其它病毒的抗病毒活性，明确其抗病毒广谱性或专一性。本项目将揭示ISGs抗CSFV的分子机制，为开发新型抗CSF策略奠定基础。

Viral infections can regulate type I interferon (IFN) response in the host, resulting in the transcription of hundreds of interferon-stimulated genes (ISGs), which in turn regulate viral replication. Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), which is a highly contagious disease that endangers the pig industry in most countries. We have previously demonstrated that several cellular proteins (such as HB) inhibit CSFV replication via the IFN signaling pathway. However, little is known about the anti-CSFV potential of ISGs and their antiviral molecular mechanisms. In this proposal, firstly, we will screen the anti-CSFV ISGs using Flow cytometry and luciferase reporter CSFV, and subsequently validate the antiviral activity of the screened ISGs in PK-15 cells using the parent CSFV. Secondly, we will focus on the interactions between the ISGs and the CSFV proteins, the regulation of the IFN signaling pathway and the specific stage(s) in the CSFV life cycle exerted by the anti-CSFV ISGs to clarify the antiviral mechanisms of the ISGs. Finally, we will testify if the anti-CSFV ISGs are able to antagonize other members within the Flaviviridae family or other important swine viruses. The project is expected to elucidate the antiviral molecular mechanisms of anti-CSFV ISGs, which will facilitate the development of anti-CSFV agents derived from the antiviral ISGs and provide new ideas and strategies for the control of CSF.