TY  - JOUR
A1  - Kleinschmidt, Malte Christian
A1  - Michaelis, Martin
A1  - Ogbomo, Henry
A1  - Doerr, Hans Wilhelm
A1  - Cinatl, Jindrich
T1  - Inhibition of apoptosis prevents West Nile virus induced cell death
T2  - BMC microbiology
N2  - 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. Pancaspase 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.
Y1  - 2007
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/925
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-44588
N1  - © 2007 Kleinschmidt et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License  (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 7
IS  - 49
SP  - 1
EP  - 8
ER  -