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 ce
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.
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Metadaten
Author:Malte C. Kleinschmidt, Martin Michaelis, Henry Ogbomo, Hans Wilhelm Doerr, Jindrich Cinatl
URN:urn:nbn:de:hebis:30-44588
Document Type:Article
Language:English
Date of Publication (online):2007/06/18
Year of first Publication:2007
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2007/06/18
Note:
© 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.
Source:BMC Microbiology 2007, 7:49. - doi:10.1186/1471-2180-7-49 ; http://www.biomedcentral.com/1471-2180/7/49/
HeBIS PPN:188421521
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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