Viroporins from RNA viruses induce caspase-dependent apoptosis

Madan, V., Castelló, A. and Carrasco, L. (2008) Viroporins from RNA viruses induce caspase-dependent apoptosis. Cellular Microbiology, 10(2), pp. 437-451. (doi: 10.1111/j.1462-5822.2007.01057.x) (PMID:17961183) (PMCID:PMC7162385)

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The virus‐encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. Here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. Synthesis of 6K protein from Sindbis virus, E from mouse hepatitis virus, M2 from influenza A virus, and 2B and 3A from poliovirus enhanced membrane permeability to different extents. We show that two proteins from hepatitis C virus, p7 and NS4A, also display viroporin activity to a level comparable to 6K protein. In addition to their capacity to disrupt ionic cellular homeostasis and promote bacterial cell lysis, the expressed viroporins were able to induce cell death. Degradation of internucleosomal DNA and generation of apoptotic bodies were observed upon viroporin expression. Consistently, cleavage of translation initiation factor 4GI and poly‐(ADP‐ribose) polymerase indicated activation of effector caspase‐3. We found that poliovirus 2B localizes partially in mitochondria and induces an anomalous perinuclear distribution of these organelles. Mitochondria morphology was also altered after expression of other viroporins. Finally, detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin‐induced apoptosis. These findings suggest that viroporins induce caspase‐dependent programmed cell death.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Castello, Professor Alfredo
Authors: Madan, V., Castelló, A., and Carrasco, L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Cellular Microbiology
ISSN (Online):1462-5822
Published Online:19 September 2007

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