内部核糖体进入位点（IRES）依赖性翻译是决定小RNA病毒和黄病毒增殖的核心步骤，挖掘病毒劫持宿主因子来服务自身IRES依赖性翻译的关键路径，将为IRES病毒的防控提供潜在靶标。我们前期以塞内卡病毒（SVV）为模式病毒，利用RNA亲和捕捉法结合质谱技术，鉴定出宿主RNA结合蛋白核仁素（NCL）与SVV 5'UTR互作，且发现NCL极有可能特异地通过参与SVV IRES依赖性翻译过程来影响SVV复制。基于此，本项目将以NCL与SVV IRES的作用关系为切入点，系统研究NCL与SVV IRES的互作和功能关系，并剖析SVV劫持NCL来服务自身IRES依赖性翻译起始的策略；同时，验证NCL对不同型IRES病毒是否存在功能保守性，并尝试筛选靶向NCL的广谱抗病毒药物。本项目不仅为认识IRES病毒的选择性翻译提供新的科学资料，亦将为相关病毒疾病的防控提供新思路和技术平台。

Internal ribosome entry site (IRES)-dependent translation is a critical step for the propagation of picornaviruses and flaviviruses. A better understanding of the virus-host interactions involving IRES-driven translation could therefore have important implications for the development of effective viral prevention or control strategies. Using the RNA affinity method followed by mass spectrometry, host RNA-binding protein nucleolin (NCL) was identified as a novel 5’UTR-interacting protein of Seneca Valley virus (SVV) that presents type III-like IRES. NCL was further confirmed to be an essential determinant for SVV infection due to its influence on the IRES activity of SVV. Based on these findings, we will unravel the interaction regions within SVV IRES and NCL and explore the effect of NCL on the SVV IRES-driven translation, and reveal the strategies employed by SVV to harness NCL for translation initiation on SVV mRNA. Furthermore, we will determine whether the regulatory function of NCL is conserved in unrelated IRES-containing viruses, and this will contribute to the screening of broad-spectrum antiviral drugs targeting NCL. Taken together, these findings not only expand our understanding of the selective translation of IRES-containing viruses, but also provide new routes to the antiviral strategies.