苜蓿银纹夜蛾核型多角体病毒(AcMNPV)在复制过程中需要将众多来自病毒和宿主的蛋白聚集于胞核内，用于核壳体装配等病毒复制过程。除部分病毒蛋白可通过自身编码核定位信号等方式入核，仍有大量病毒蛋白发生核聚集的机制未知。.CRM1是最重要的蛋白出核转运受体之一。我们前期发现AcMNPV可以通过Ac34阻断CRM1通路，从而导致病毒复制所需的宿主蛋白在核内滞留、聚集(PLoS Pathog. 2016 Nov 1)。由于生物信息学预测发现大量AcMNPV蛋白含有潜在的CRM1靶序列，提示我们从出核转运受阻这一全新角度去探索病毒蛋白发生核聚集的原因。我们将利用既有的AcMNPV ORF文库来识别因CRM1出核转运受阻而发生核聚集的病毒蛋白，并探索Ac34阻断CRM1通路的分子机制。鉴于AcMNPV是迄今发现的唯一一种特异性阻断CRM1通路的病毒，该研究必将深化我们对病毒调控细胞物质运输机器的认识。

As a nucleopolyhedrovirus, Autographa californica Multiple Nucleopolyhedrovirus (AcMNPV) replication is accompanied by nuclear accumulation of a variety of viral and cellular proteins, which is required for nucleocapsid assembly in the nucleus. Except for a limited number of viral proteins, of which nuclear accumulation mechanisms are previously identified, how most viral proteins relocate to the nucleus during AcMNPV infection remains obscure...Chromosomal maintenance 1 (CRM1) is the most important exportin in eukaryotic cells, and mediates the nuclear export of protein bearing leucine-rich nuclear export sequence (NES). Bioinformatics assay showed that many viral proteins contain putative NESes, and are supposed to be exported from the nucleus through the CRM1-dependent pathway. This finding suggested that AcMNPV may suppress the CRM1-dependent nuclear export, which leads to NES-bearing proteins accumulating in the nucleus, and eventually participating in nucleocapsid assembly process...Our published data demonstrated that the CRM1-dependent nuclear export is inhibited during AcMNPV infection, and viral late gene product Ac34 is responsible for the inhibition (PLoS Pathog. 2016 Nov 1). In this project, we will continue to investigate the impact of Ac34 on virus-induced protein nuclear accumulation and the molecular mechanism of how Ac34 suppressing CRM1 nuclear export. Since AcMNPV is the only virus that specifically inhibiting CRM1, unveiling its inhibition mechanism and significance will shed light on how virus interferes and harnesses host material transport mechinery.