Zhu Jie, Wang Binbin, Miao Qiuhong, Tan Yonggui, Li Chuanfeng, Chen Zongyan, Guo Huimin, Liu Guangqing
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, 200241, China.
PLoS One. 2015 Nov 23;10(11):e0143467. doi: 10.1371/journal.pone.0143467. eCollection 2015.
Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.
兔出血症病毒（RHDV）是兔出血症的病原体，是杯状病毒科的重要成员。目前，尚无合适的组织培养系统可用于增殖RHDV，这限制了对RHDV发病机制的研究。此外，与其他杯状病毒科病毒相比，RHDV翻译和复制的潜在机制在很大程度上尚不清楚。我们实验室最近构建的RHDV复制子提供了一个合适的模型，可用于在不进行体外RHDV繁殖和培养的情况下研究RHDV的发病机制。利用这个RHDV复制子，我们首次证明病毒基因组连接蛋白（VPg）对于RK-13细胞中RHDV的翻译至关重要。此外，我们表明VPg在体内和体外与真核起始因子4E（eIF4E）相互作用，并且eIF4E沉默会抑制RHDV翻译，这表明VPg与eIF4E之间的相互作用参与了RHDV翻译。我们的结果支持这样的假设，即VPg在RHDV翻译起始过程中作为一种新型的帽替代物发挥作用。
