Nonstructural protein 6 of porcine epidemic diarrhea virus induces autophagy to promote viral replication via the PI3K/Akt/mTOR axis
文献类型: 外文期刊
作者: Lin, Huixing 1 ; Li, Bin 2 ; Liu, Mingxing 1 ; Zhou, Hong 1 ; He, Kongwang 2 ; Fan, Hongjie 1 ;
作者机构: 1.Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Peoples R China
2.Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing 210014, Peoples R China
3.Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China
关键词: Porcine epidemic diarrhea virus; Nonstructural protein 6; Autophagy; Replication
期刊名称:VETERINARY MICROBIOLOGY ( 影响因子:3.293; 五年影响因子:3.599 )
ISSN: 0378-1135
年卷期: 2020 年 244 卷
页码:
收录情况: SCI
摘要: Porcine epidemic diarrhea virus (PEDV) has caused, and continues to cause, severe economic losses to the swine industry worldwide. The pathogenic mechanism and immune regulatory interactions between PEDV and the host remain largely unknown. In this study, the interaction between autophagy and PEDV replication in intestinal porcine epithelial (IPEC-J2) cells was investigated. The effects of the structural and nonstructural proteins of PEDV on the autophagy process and the autophagy-related signaling pathways were also examined. The results shown that PEDV replication increased the autophagy flux in IPEC-J2 cells, and that autophagy was beneficial to PEDV replication, which may be one of the reasons for the rapid damage to intestinal epithelial cells and the enhanced virulence of PEDV in both newborn piglets and finishing pigs. When autophagy was pharmacologically induced by rapamycin, PEDV replication increased from 8.5 x 10(5) TCID50/mL to 8.8 x 10(6) TCID50/mL in IPEC-J2 cells. When autophagy was pharmacologically suppressed by hydroxychloroquine, PEDV replication decreased from 8.5 x 10(5) TCID50/mL to 7.9 x 10(4) TCID50/mL. To identify which PEDV proteins were the key inducers of autophagy, all 4 structural proteins and 17 nonstructural proteins of PEDV were eukaryotic expressed. It was found that the nonstructural protein 6 (nsp6) and ORF3 of PEDV were able to induce significant autophagy in IPEC-J2 cells, but the other proteins were unable to induce autophagy. It was indicated that nsp6-induced autophagy mainly occurred via the PI3K/Akt/mTOR signaling pathway. The results accelerate the understanding of the biology and pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.
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