Data_Sheet_1_Proteomic Investigation Reveals Eukaryotic Translation Initiation Factor 5A Involvement in Porcine Reproductive and Respiratory Syndrome Virus Infection in vitro.DOCX

Porcine reproductive and respiratory syndrome virus (PRRSV), one of the most serious animal pathogens in the world, has caused enormous global swine industry losses. An in-depth investigation of the PRRSV-host interaction would be beneficial for preventing and controlling PRRSV infections and transmission. In this study, we performed label-free quantitative proteomic assays to investigate proteome dynamics of porcine alveolar macrophages (PAMs) during infection with highly pathogenic PRRSV (HP-PRRSV) strain HN07-1. Analysis of the results led to identification of 269 significantly differentially expressed host cellular proteins, of which levels of proteins belonging to the eukaryotic translation initiation factor (eIF) family were found to be decreased in abundance in HP-PRRSV-infected PAMs. Furthermore, knockdown of eIF5A expression was demonstrated to markedly suppress HP-PRRSV propagation, as reflected by reduced progeny virus titers in vitro. These results highlight the importance of eIF5A in PRRSV infection, while also demonstrating that PAMs down-regulate eIF5A expression as a host cell antiviral strategy. Results of the current study deepen our understanding of PRRSV pathogenesis and provide novel insights to guide development of effective strategies to combat the virus.

猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus, PRRSV）是全球危害最为严重的动物病原体之一，已给全球养猪业造成了巨额经济损失。深入解析PRRSV与宿主的相互作用，对于防控PRRSV的感染与传播具有重要意义。本研究采用无标记定量蛋白质组学检测方法，探究了高致病性PRRSV（HP-PRRSV）毒株HN07-1感染猪肺泡巨噬细胞（porcine alveolar macrophages, PAMs）过程中的蛋白质组动态变化。通过对实验结果的分析，共鉴定得到269个显著差异表达的宿主细胞蛋白，其中真核翻译起始因子（eukaryotic translation initiation factor, eIF）家族蛋白在HP-PRRSV感染的PAMs中丰度显著下调。进一步研究证实，敲低eIF5A的表达可显著抑制HP-PRRSV的增殖，体外实验中表现为子代病毒滴度的降低。本研究结果凸显了eIF5A在PRRSV感染过程中的关键作用，同时证实宿主细胞可通过下调eIF5A的表达实现抗病毒防御策略。本研究加深了我们对PRRSV致病机制的理解，也为开发高效抗PRRSV防控策略提供了全新的研究思路。