title: Inhibition of apoptosis prevents West Nile virus induced cell death.
abstract: BACKGROUND
  West Nile virus (WNV) infection can cause severe meningitis and encephalitis in humans. Apoptosis was recently shown to contribute to the pathogenesis of WNV encephalitis. Here, we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells.
  
  
  RESULTS
  T98G cells are highly permissive for lytic WNV-infection as demonstrated by the production of infectious virus titre and the development of a characteristic cytopathic effect. WNV replication decreased cell viability and induced apoptosis as indicated by the activation of the effector caspase-3, the initiator caspases-8 and -9, poly(ADP-ribose)polymerase (PARP) cleavage and the release of cytochrome c from the mitochondria. Truncation of BID indicated cross-talk between the extrinsic and intrinsic apoptotic pathways. Inhibition of the caspases-8 or -9 inhibited PARP cleavage, demonstrating that both caspases are involved in WNV-induced apoptosis. Pan-caspase inhibition prevented WNV-induced apoptosis without affecting virus replication.
  
  
  CONCLUSIONS
  We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death.
authors.affiliation: Institute for Medical Virology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. malte-kleinschmidt@gmx.de <malte-kleinschmidt@gmx.de>
authors.forename: Malte C
authors.initials: MC
authors.lastname: Kleinschmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Henry
authors.initials: H
authors.lastname: Ogbomo
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival; D002522:Chlorocebus aethiops; D045304:Cytochromes c / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma; D006801:Humans; D014709:Vero Cells; D014779:Virus Replication; D014902:West Nile virus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D045304:Cytochromes c