Inhibition of apoptosis prevents West Nile virus induced cell death.
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.
Kleinschmidt
Malte C
MC
Institute for Medical Virology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. malte-kleinschmidt@gmx.de <malte-kleinschmidt@gmx.de>
Michaelis
Martin
M
Ogbomo
Henry
H
Doerr
Hans-Wilhelm
HW
Cinatl
Jindrich
J
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
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D045304:Cytochromes c