title: Bovine herpes virus type 1 induces apoptosis through Fas-dependent and mitochondria-controlled manner in Madin-Darby bovine kidney cells.
abstract: BACKGROUND
  Bovine herpesvirus type 1 (BHV-1) is an important pathogen in cattle that is responsible for substantial economic losses. Previous studies suggest that BHV-1 may induce apoptosis in Madin-Darby bovine kidney (MDBK) cells via a mechanism only involving caspases and p53. However, the mechanism for BHV-1-induced MDBK cell apoptosis still requires more research.
  
  
  METHODS
  MDBK was used as a model to study the precise signaling pathways of apoptosis induced by BHV-1 infection.
  
  
  RESULTS
  BHV-1 infection activated a Fas/FasL-mediated apoptotic pathway, resulting in activation of caspase-8 and cleavage of Bid. In addition, BHV-1 infection down-regulated Bcl-2 and up-regulated Bax expression, thereby initiating the release of cytochrome c followed by caspase-9 activation. The combined activation of the extrinsic and intrinsic pathways resulted in activation of downstream effecter caspase-3 and poly ADP-ribose polymerase (PARP), leading to apoptosis. Furthermore, blocking apoptosis using caspase inhibitors improved BHV-1-infected MDBK cell viability to different extent. BHV-1 infection did not induce significant DNA fragmentation in MDBK cells pretreated with ammonium chloride (NH4Cl) or cells infected with UV-inactivated BHV-1. Blocking caspases activation increased BHV-1 replication.
  
  
  CONCLUSIONS
  BHV-1 induces apoptosis in MDBK cells through extrinsic and intrinsic pathways and there might be cross-talk between the two pathways. In addition, BHV-1 replication may be necessary for the induction of apoptosis in BHV-1-infected cells, and prolonged cell viability benefits BHV-1 replication.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, PR China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.forename: Kuan
authors.initials: K
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Guangda
authors.initials: G
authors.lastname: Chen
authors.forename: Honglei
authors.initials: H
authors.lastname: Zhang
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000378:metabolism; D007242:Herpesvirus 1, Bovine / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9