Abstract
Varicella-zoster virus infects multiple human and monkey cells in culture. The mode of cell death appears to be autophagy or apoptosis. Analysis of VZV-infected human melanoma (MeWo) cells revealed that Bcl-2 mRNA and protein levels were decreased significantly 64 and 72 hpi (hours post infection), accompanied by the release of cytochrome c from mitochondria into the cytoplasm. Western blot analysis of virus-infected cells revealed activation of caspase-8, a marker for the extrinsic pathway of apoptosis, and caspase-9, a marker for the intrinsic pathway of apoptosis at 64 and 72 hpi. Significant increases in the levels of cleaved caspase-3 and cleaved poly (ADP) ribose polymerase (PARP) were also seen at the height of cytopathic effect. Thus VZV induces apoptosis in MeWo cells in which Bcl-2 is down-regulated. Future studies will determine differences in the cascade of apoptotic events in non-neuronal cells compared to neurons that allow VZV to become latent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ashkenazi A, Dixit VM (1998). Death receptors: signaling and modulation. Science 281: 1305–1308.
Gilden DH, Vafai A, Shtram Y, Becker Y, Devlin M, Wellish M (1983). Varicella-zoster virus DNA in human sensory ganglia. Nature 306: 478–480.
Green DR, Reed JC (1998). Mitochondria and apoptosis. Science 281: 1309–1312.
Hood C, Cunningham AL, Slobedman B, Boadie RA, Abendroth A (2003). Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: evidence for a celltype-specific apoptotic response. J Virol 77: 12852–12864.
Huang DC, Strasser A (2000). BH3-only proteins-essential initiators of apoptotic cell death. Cell 103: 839–842.
König A, Homme C, Hauröder B, Dietrich A, Wolff MH (2003). The varicella-zoster virus induces apoptosis in vitro in subpopulations of primary human peripheral blood mononuclear cells. Microbes Infect 5: 879–989.
Mahalingam R, Wellish M, Wolf W, Dueland AN, Cohrs R, Vafai A, Gilden DH (1990). Latent varicella-zoster virus DNA in human trigeminal and thoracic ganglia. N Engl J Med 323: 627–630.
Mahalingam R, Wellish M, Dueland AN, Cohrs R, Gilden DH (1992). Localization of herpes simplex virus type 1 and varicella-zoster virus in human ganglia. Ann Neurol 31: 444–448.
Pignata C, Fiore M, de Filipppo S, Cavalcanti M, Gaetaniello L, Scotese I (1998). Apoptosis as a mechanism of peripheral blood mononuclear cell death after measles and varicella-zoster virus infections in children. Pediatr Res 43: 77–83.
Pugazhenthi S, Miller E, Sable C, Young P, Heidenreich KA, Boxer LM, Reusch JE (1999). Insulin-like growth factor-I induces bcl-2 promoter through the transcription factor cAMP-response element-binding protein. J Biol Chem 274: 27529–27535.
Pugazhenthi S, Gilden DH, Nair S, McAdoo A, Wellish M, Brazeau E, Mahalingam R (2009). Simian varicella virus induces apoptosis in monkey kidney cells by the intrinsic pathway and involves downregulation of Bcl-2 expression. J Virol 83: 9273–9282.
Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE (2000). Akt/protein kinase B up-regulates Bcl-2 expression through cAMPresponse element-binding protein. J Biol Chem 275: 10761–10766.
Sadzot-Delvaux C, Thonard P, Schoonbroodt S, Piette J, Rentier B (1995). Varicella-zoster virus induces apoptosis in cell culture. J Gen Virol 76: 2875–2879.
Stennicke HR, Salvesen GS (1998). Properties of the caspases. Biochim Biophys Acta 1387: 17–31.
Takahashi MN, Jackson W, Laird DT, Culp TD, Grose, C, Haynes II, JI, Benetti L (2009). Varicella-zoster virus infection induces autophagy in both cultured cells and human skin vesicles. J Virol 83: 5466–5476.
Tischer BK., Kaufer B, Sommer M, Wussow F, Arvin AM, Osterrieder N (2007). A self-excisable infectious bacterial artificial chromosome clone of varicella-zoster virus allows analysis of the essential tegument protein encoded by ORF9. J Virol 81: 13200–13208.
Tischer BK, von Einem J, Kaufer B, Osterrieder N (2006). Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli. Biotechniques 40: 191–197.
Vaux DL, Haecker G, Strasser A (1994). An evolutionary perspective on apoptosis. Cell 76: 777–779.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported in part by Public Health Service grants NS032623 and AG006127 (D.H.G. and R.M.) and AG032958 (D.H.G., R.M., S.P.) from the National Institutes of Health. Elizabeth Brazeau was supported by NIH Public Health Service Training Grant NS007321. The authors thank Dr. Randall Cohrs for useful discussions and Cathy Allen for manuscript preparation.
Rights and permissions
About this article
Cite this article
Brazeau, E., Mahalingam, R., Gilden, D. et al. Varicella-zoster virus—induced apoptosis in MeWo cells is accompanied by down-regulation of Bcl-2 expression. Journal of NeuroVirology 16, 133–140 (2010). https://doi.org/10.3109/13550281003682547
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.3109/13550281003682547