title: Porcine reproductive and respiratory syndrome virus triggers mitochondrial fission and mitophagy to attenuate apoptosis.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) causes acute mitochondrial dysfunction by elevating the level of reactive oxygen species. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial homeostasis. Here we show that PRRSV infection stimulated mitochondrial fission and mitophagy to attenuate apoptosis in Marc145 cells. PRRSV infection induced the expression of Drp1, enhanced phosphorylation of Drp1 at Ser616 and its subsequent translocation to mitochondria. Furthermore, PRRSV infection increased the expression of PINK1 and Parkin and also stimulated the recruitment of Parkin to mitochondria. In addition, a sensitive dual fluorescence vector expressing mito-mRFP-EGFP targeted mitochondria was employed to observe the complete mitophagy by delivering dysfunctional mitochondria to lysosome for degradation. Interfering the expression of Drp1 and or Parkin suppressed PRRSV replication. More importantly, silencing of Drp1 or Parkin caused significant elevation in apoptotic signaling. These results suggest that PRRSV infection stimulates mitochondrial fission and mitophagy to facilitate virus replication most probably by attenuating apoptosis.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Shuaifeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Faheem Ahmed
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002522:Chlorocebus aethiops; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D063306:Mitophagy; D010766:Phosphorylation; D019318:Porcine Reproductive and Respiratory Syndrome / Q000473:pathology* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D034281:Dynamins
keywords: PRRSV; Pathology Section; apoptosis; mitochondrial fission; mitophagy