Wang Jianmin, Du Jiang, Jin Qi
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
PLoS One. 2014 Jun 9;9(6):e99768. doi: 10.1371/journal.pone.0099768. eCollection 2014.
Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.
肠道病毒71型是婴幼儿手足口病的主要病原体之一。肠道病毒71型的复制依赖于宿主细胞因子。病毒复制复合体在新的细胞质囊泡区室中形成。病毒劫持了哪些细胞途径来形成这些囊泡尚不清楚。在此，我们研究了与细胞分泌途径相关的蛋白质是否参与肠道病毒71型的复制。我们使用了基于小干扰RNA的功能丧失分析方法。我们发现肠道病毒71型RNA复制依赖于I类ADP核糖基化因子的活性。同时缺失ADP核糖基化因子1和3（而非其他三种）会抑制细胞中的病毒复制。我们还用各种技术证明，布雷菲德菌素A敏感的鸟苷酸交换因子GBF1对肠道病毒71型复制至关重要。我们的结果表明，肠道病毒71型复制依赖于GBF1介导的I类ADP核糖基化因子的激活。这些结果揭示了肠道病毒71型复制与细胞分泌途径之间的联系；该途径可能代表抗病毒治疗的新靶点。
