Summary
Subversion of the host response to virus infection is a universal theme of virology and viral immunology. Multiple mechanisms are in place to limit virus spread on behalf of the host, yet through evolution, viruses have adapted to either weaken or eliminate the effects of these host factors. Cell death or apoptosis is one such example of a host response to viral infection. As such, experimental techniques that enable analysis of viruses (and viral genes) involved in triggering, blocking, or perhaps augmenting this process represent important tools for virologists, immunologists, and cell biologists. Presented here are a series of techniques developed in our lab for the analysis of apoptosis that occurs as a consequence of herpes simplex virus type 1 infection.
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Notes
- 1.
Alternatively, if antibodies containing HRP are utilized during the immunoblotting procedure, traditional methods of detection such as ECL may be substituted here.
References
Yedowitz, J. C., and Blaho, J. A. (2005). Herpes simplex virus 2 modulates apoptosis and stimulates NF-kappaB nuclear translocation during infection in human epithelial HEp-2 cells, Virology 342, 297–310.
Whitley, R. J. (2001). in Fields Virology (Roizman, B., and Knipe, D. M., Eds.), pp. 2462–2498, Lippincott-Raven, Philadelphia, PA.
Qian, H., and Atherton, S. (2003). Apoptosis and increased expression of Fas ligand after uniocular anterior chamber (AC) inoculation of HSV-1, Curr Eye Res 26, 195–203.
Wilson, S. E., Pedroza, L., Beuerman, R., and Hill, J. M. (1997). Herpes simplex virus type-1 infection of corneal epithelial cells induces apoptosis of the underlying keratocytes, Exp Eye Res 64, 775–779.
Miles, D., Athmanathan, S., Thakur, A., and Willcox, M. (2003). A novel apoptotic interaction between HSV-1 and human corneal epithelial cells, Curr Eye Res 26, 165–174.
DeBiasi, R. L., Kleinschmidt-DeMasters, B. K., Richardson-Burns, S., and Tyler, K. L. (2002). Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis, J Infect Dis 186, 1547–1557.
Perkins, D., Gyure, K. A., Pereira, E. F., and Aurelian, L. (2003). Herpes simplex virus type 1-induced encephalitis has an apoptotic component associated with activation of c-Jun N-terminal kinase, J Neurovirol 9, 101–111.
Koyama, A. H., and Adachi, A. (1997). Induction of apoptosis by herpes simplex virus type 1, J Gen Virol 78, 2909–2912.
Jerome, K. R., Chen, Z., Lang, R., Torres, M. R., Hofmeister, J., Smith, S., Fox, R., Froelich, C. J., and Corey, L. (2001). HSV and glycoprotein J inhibit caspase activation and apoptosis induced by granzyme B or Fas, J Immunol 167, 3928–3935.
Aubert, M., and Blaho, J. A. (1999). The herpes simplex virus type 1 regulatory protein ICP27 is required for the prevention of apoptosis in infected human cells, J Virol 73, 2803–2813.
Gautier, I., Coppey, J., and Durieux, C. (2003). Early apoptosis-related changes triggered by HSV-1 in individual neuronlike cells, Exp Cell Res 289, 174–183.
Kraft, R. M., Nguyen, M. L., Yang, X. H., Thor, A. D., and Blaho, J. A. (2006). Caspase 3 activation during herpes simplex virus 1 infection, Virus Res 120, 163–175.
Nguyen, M. L., Kraft, R. M., and Blaho, J. A. (2005). African green monkey kidney Vero cells require de novo protein synthesis for efficient herpes simplex virus 1-dependent apoptosis, Virology 336, 274–290.
Koyama, A. H., and Miwa, Y. (1997). Suppression of apoptotic DNA fragmentation in herpes simplex virus type 1-infected cells, J Virol 71, 2567–2571.
Aubert, M., O’Toole, J., and Blaho, J. A. (1999). Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1, J Virol 73, 10359–10370.
Galvan, V., and Roizman, B. (1998). Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell- type-dependent manner, Proc Natl Acad Sci USA 95, 3931–3936.
Jerome, K. R., Fox, R., Chen, Z., Sears, A. E., Lee, H., and Corey, L. (1999). Herpes simplex virus inhibits apoptosis through the action of two genes, Us5 and Us3, J Virol 73, 8950–8957.
Jerome, K. R., Fox, R., Chen, Z., Sarkar, P., and Corey, L. (2001). Inhibition of apoptosis by primary isolates of herpes simplex virus, Arch Virol 146, 2219–2225.
Nguyen, M. L., and Blaho, J. A. (2007). Apoptosis during herpes simplex virus infection, Adv Virus Res 69, 67–97.
Moore, A. E., Sabachewsky, L., and Toolan, H. W. (1955). Culture characteristics of four permanent lines of human cancer cells, Cancer Res. 15, 598–605.
Nelson-Rees, W. A., Zhdanov, V. M., Hawthorne, P. K., and Flandermeyer, R. R. (1974). HeLa-like marker chromosomes and type-A variant glucose-6-phosphate dehydrogenase isoenzyme in human cell cultures producing Mason-Pfizer monkey virus-like particles, J Natl Cancer Inst 53, 751–757.
Chen, T. R. (1988). Re-evaluation of HeLa, HeLa S3, and HEp-2 karyotypes, Cytogenet Cell Genet 48, 19–24.
Roizman, B. (1962). Polykaryocytosis induced by viruses, Proc Natl Acad Sci USA 48, 228–234.
Avitabile, E., Di Gaeta, S., Torrisi, M. R., Ward, P. L., Roizman, B., and Campadelli-Fiume, G. (1995). Redistribution of microtubules and Golgi apparatus in herpes simplex virus-infected cells and their role in viral exocytosis, J Virol 69, 7472–7482.
Heeg, U., Dienes, H. P., Muller, S., and Falke, D. (1986). Involvement of actin-containing microfilaments in HSV-induced cytopathology and the influence of inhibitors of glycosylation, Arch Virol 91, 257–270.
Roizman, B., and Roanne, P. R. (1964). Multiplication of herpes simplex virus. II. The relationship between protein synthesis and the duplication of viral DNA in infected HEp-2 cells, Virology 22, 262–269.
Roizman, B., and Furlong, D. (1974). in Comprehensive Virology (Fraenkel-Conrat, H., and Wagner, R. R., Eds.), pp. 229–403, Plenum, New York, NY.
Goodkin, M. L., Morton, E. R., and Blaho, J. A. (2004). Herpes simplex virus infection and apoptosis, Intl Rev Immunol 23, 141–172.
Blaho, J. A. (2004). Virus infection and apoptosis (issue II) an introduction: cheating death or death as a fact of life?, Int Rev Immunol 23, 1–6.
Hampar, B., and S. A. Elison. (1961). Chromosomal aberrations induced by an animal virus, Nature 192, 145–147.
Aubert, M., Rice, S. A., and Blaho, J. A. (2001). Accumulation of herpes simplex virus type 1 early and leaky-late proteins correlates with apoptosis prevention in infected human HEp-2 cells, J Virol 75, 1013–1030.
Liu, X., Zou, H., Slaughter, C., and Wang, X. (1997). DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis, Cell 89, 175.
Aubert, M., Pomeranz, L. E., and Blaho, J. A. (2007). HSV blocks apoptosis by precluding mitochondrial cytochrome c release independent of caspase activation in infected human epithelial cells, Apoptosis 12, 19–35.
Cryns, V., and Yuan, J. (1998). Proteases to die for, Genes Dev 12, 1551–1570.
Green, D. R. (1998). Apoptotic pathways: the roads to ruin, Cell 94, 695–698.
Salvesen, G. S., and Dixit, V. M. (1997). Caspases: intracellular signaling by proteolysis, Cell 91, 443–446.
Vaux, D. L., and Strasser, A. (1996). The molecular biology of apoptosis, Proc Natl Acad Sci USA 93, 2239–2244.
Wasilenko, S. T., Meyers, A. F., Vander Helm, K., and Barry, M. (2001). Vaccinia virus infection disarms the mitochondrion-mediated pathway of the apoptotic cascade by modulating the permeability transition pore, J Virol 75, 11437–11448.
Green, D. R., and Reed, J. C. (1998). Mitochondria and apoptosis, Science 281, 1309–1312.
Petit, P. X., Susin, S. A., Zamzami, N., Mignotte, B., and Kroemer, G. (1996). Mitochondria and programmed cell death: back to the future, FEBS Lett 396, 7–13.
Qian, T., Nieminen, A. L., Herman, B., and Lemasters, J. J. (1997). Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes, Am J Physiol 273, C1783–C1792.
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade, Cell 91, 479–489.
Blaho, J. A., Morton, E. R., and Yedowitz, J. C. (2005). Herpes Simplex Virus: Propagation, Quantification, and Storage, Curr Protoc Microbiol 14E, 1–23.
Nguyen, M. L., Kraft, R. M., and Blaho, J. A. (2007). Susceptibility of cancer cells to herpes simplex virus-dependent apoptosis, J Gen Virol 88, 1866–1875.
Aubert, M., and Blaho, J. A. (2001). Modulation of apoptosis during herpes simplex virus infection in human cells, Microbes Infect 3, 859–866.
Sanfilippo, C. M., and Blaho, J. A. (2006). ICP0 gene expression is a herpes simplex virus type 1 apoptotic trigger, J Virol 80, 6810–6821.
Blaho, J. A., and Roizman, B. (1998). in Methods in Molecular Medicine: Herpes Simplex Virus Protocols (Brown, S. M., and Maclean, A. R., Eds.), pp. 237–256, Human Press, Totowa, NJ.
Brown, S. M., and MacLean, A. R., Eds. (1998). Herpes Simplex Virus Protocols: Methods in Molecular Medicine, Vol. 10, Human Press, Totowa, NJ.
Blaho, J. A., Mitchell, C., and Roizman, B. (1993). Guanylylation and adenylylation of the alpha regulatory proteins of herpes simplex virus require a viral beta or gamma function, J Virol 67, 3891–3900.
Blaho, J. A., Zong, C. S., and Mortimer, K. A. (1997). Tyrosine phosphorylation of the herpes simplex virus type 1 regulatory protein ICP22 and a cellular protein which shares antigenic determinants with ICP22, J Virol 71, 9828–9832.
Yedowitz, J. C., Kotsakis, A., Schlegel, E. F., and Blaho, J. A. (2005). Nuclear localizations of the herpes simplex virus type 1 tegument proteins VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization and VP22 nuclear import, J Virol 79, 4730–4743.
Kotsakis, A., Pomeranz, L. E., Blouin, A., and Blaho, J. A. (2001). Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein, J Virol 75, 8697–8711.
Acknowledgments
We wish to thank all of the individuals in our laboratory whose hard work has set the basis for developing this interesting new research project. Individuals who played significant roles in generating the protocols and the methodologies that served as the basis of this review include Martine Aubert, Jennifer O’Toole, Renee Baranin, Lisa Pomeranz, Christine Sanfilippo, Renzo Lambardozzi, Natalie Chirimuuta, Margot Goodkin, Elise Morton, Jamie Yedowitz, Marie Nguyen, Rachel Kraft, Kristen Pena, Elisabeth Gennis, Fatima Manzoor, and Leah Kang. These studies were supported in part by grants from the United States Public Health Service (AI38873 and AI48582 to J.A.B.) and the American Cancer Society (JFRA 634 to J.A.B.). J.A. Blaho thanks the Lucille P. Markey Charitable Trust and the National Foundation for Infectious Diseases for their support. C. Cotter is a predoctoral trainee and was supported in part by a United States Public Health Service Institutional Research Training Award (AI 07647).
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Cotter, C.R., Blaho, J.A. (2009). Detection of Herpes Simplex Virus Dependent Apoptosis. In: Erhardt, P., Toth, A. (eds) Apoptosis. Methods in Molecular Biology, vol 559. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-017-5_26
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DOI: https://doi.org/10.1007/978-1-60327-017-5_26
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