猪繁殖与呼吸综合征病毒感染对世界养猪业造成重大经济损失。目前疫苗不能有效控制该病的发生。对该病的有效控制很大程度上依赖对病毒和宿主相互作用机制的了解。DEAD-box RNA解旋酶是宿主细胞中广泛存在的蛋白。该家族的DDX3和DDX5与HIV、HBV、HCV、流感病毒感染有关，但具体机制仍不清楚。我们的初步研究结果表明这两个蛋白与PRRSV病毒的感染有关，过量表达会抑制病毒增殖，而抑制表达会促进病毒增殖。本项目拟借助病毒学和细胞生物学的方法在MARC-145和PAM-pCD163细胞上研究DDX3和DDX5与病毒相互作用影响病毒增殖的机制，以及病毒蛋白与DDX3相互作用对干扰素产生的影响。并借助蛋白质结晶学方法研究DDX3或DDX5与病毒蛋白复合物的空间结构，从结构上明确宿主蛋白与病毒蛋白的相互作用方式。本研究将促进对PRRSV增殖机制的了解，对寻找新的抗PRRSV感染的方法具有重要意义。

Porcine reproductive and respiratory syndrome virus continues to cause economically significant impacts on the swine industry worldwide. Unfortunately, the conventional vaccines fail to provide sustainable disease control. Therefore, the successful control of the disease relies tremendously on the basic knowledge of host-virus interactions. DEAD-box RNA helicases are expressed ubiquitously in host cell. Members of this family of protein DDX3 and DDX5 have been shown to participate in several viruses replication, including HIV, HBV, HIV and influenza virus. Our preliminary data showed that overexpression of these two proteins inhibit PRRSV propagation, while decrease of DDX3 and DDX5 expression by RNA interference facilitates virus propagation. Therefore, in this project, we plan to continue the studies on the interactions between DDX3,DDX5 and virus and on how the interactions between viral protein(s) and DDX3 influence interferon production in MARC-145 and PAM-pCD163 cells by using virology and cell biology methods. Furthermore, we will determine the crystal structures of DDX3 or DDX5 with viral proteins to provide more information on the interactions between these proteins. The studies on DDX3 and DDX5 will help us to clarify their roles in PRRSV infection,which will also provide more insights in the molecular mechanisms of PRRSV replication and the novel strategies to control PRRSV infection.