Wang Kai, Li Shuaifeng, Worku Tesfaye, Hao Xingjie, Yang Liaohan, Zhang Shujun
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, Hubei, PR China.
Biochem Biophys Res Commun. 2017 Oct 14;492(2):236-242. doi: 10.1016/j.bbrc.2017.08.057. Epub 2017 Aug 16.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and Landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of the convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear. In this study, we demonstrated that PRRSV infection induced complete autophagy and up-regulated the expression of Rab11a. Furthermore, interference of the expression of Rab11a resulted in the accumulation of endogenous LC3-II and p62, indicating that Rab11a played a vital role in autophagosome maturation. Silencing of Rab11a resulted in a compromise the expression of intracellular viral NSP2 and ORF7. Besides, confocal microscopy analysis showed that viral NSP2 was colocalized with Rab11a in Marc145 cells. Collectively, our findings revealed that Rab11a acted as a proviral host factor that benefited PRRSV replication in a manner that correlates with autophagy.
猪繁殖与呼吸综合征病毒(PRRSV)是已知在全球养猪业造成巨大经济损失的主要病毒。在我们之前的研究中,对具有高致病性PRRSV(HP-PRRSV)易感性差异的桐城猪和兰德瑞斯猪的PRRSV感染肺组织进行转录谱分析,结果显示Rab11a存在差异表达。小GTP酶Rab11a调节参与自噬的细胞内膜运输事件。然而,在PRRSV感染期间内体Rab11a与自噬途径的交汇情况仍不清楚。在本研究中,我们证明PRRSV感染诱导了完全自噬并上调了Rab11a的表达。此外,干扰Rab11a的表达导致内源性LC3-II和p62的积累,表明Rab11a在自噬体成熟中起关键作用。沉默Rab11a导致细胞内病毒NSP2和ORF7的表达受损。此外,共聚焦显微镜分析显示病毒NSP2与Marc145细胞中的Rab11a共定位。总的来说,我们的研究结果表明Rab11a作为一种前病毒宿主因子,以与自噬相关的方式促进PRRSV复制。