Abstract
Specific cellular and temporal regulation of gene expression is a goal of many molecular studies. The study of programmed cell death requires cellular specificity, temporal regulation, as well as the interaction of a myriad of gene products. One way to regulate these interactions in an apoptotic cell is by specifically altering gene expression using a DNA transfer system. Several methods exist that are capable of delivering gene constructs into intact animals. DNA can be introduced into cells by direct DNA transfer using liposome-encapsulated DNA or viral vector systems which carry the gene of interest. An ex vivo approach can be implemented whereby cells are manipulated to produce the desired gene product and subsequently transferred to the animal. Transfer can also be accomplished using viral vector systems. In particular, transfer into the central nervous system and neurons is most commonly accomplished using various viral vector systems. Our laboratory and others have been developing herpes simplex virus (HSV) amplicon vectors, which are plasmid-based vectors that carry the gene of interest under the control of a specific promoter. In this chapter, we will review HSV amplicon vectors as a modality for gene transfer in two models of apoptosis, central nervous system (CNS) ischemia and cochlear degeneration. Improved helper-free amplicon methodology will be described, as well as advantages and disadvantages associated with this viral vector system.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Federoff, H. J., Geschwind, M. D., Geller, A. I., and Kessler, J. A. (1992) Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. Proc. Natl. Acad. Sci. USA 89(5), 1636–1640.
Frenkel, N. (1981) Defective interfering herpesviruses, in The Human Herpes-viruses-An Interdisciplinary Prospective (Nahmias, A., Dowdle, W., and Scchinazy, R., eds.), Elsevier-North Holland, New York, pp.91–120.
Frenkel, N., Spaete, R. R., Vlazny, D. A., Deiss, L. P., and Locker, H. (1982) The herpes simplex virus amplicon-a novel animal-virus cloning vector, in Eucaryotic Viral Vectors (Gluzman, Y., ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 205–209.
Geller, A. I. and Breakefield, X. O. (1988) A defective HSV-1 vector expresses Escherichia coli β-galactosidase in cultured peripheral neurons. Science 241, 1667–1669.
Geller, A. I., Keyomarsi, K., Bryan, J., and Pardee, A. B. (1990) An efficient deletion mutant packaging system for defective herpes simplex virus vectors: potential applications to human gene therapy and neuronal physiology. Proc. Natl. Acad. Sci. USA 87, 8950–8954.
Geschwind, M. D., Hartnick, C. J., Liu, W., Amat, J., Van De Water, T. R., and Federoff, H. J. (1996) Defective HSV-1 vector expressing BDNF in auditory ganglia elicits neurite outgrowth: model for treatment of neuron loss following cochlear degeneration. Hum. Gene Ther. 7 173–182.
Geschwind, M. D., Lu, B., and Federoff, H. J. (1994) Expression of neuro-trophic genes from herpes simplex virus type 1 vectors: modifying neuronal phenotype. Meth. Neurosci. 21, 462–482.
Lawrence, M., Ho, D., Dash, R., and Sapolsky, R. (1995) Herpes simplex virus overexpressing the glucose transporter gene protect against seisure-induced neuron loss. Proc. Natl. Acad. Sci. USA 92, 7247–7251.
Spaete, R. R. and Frenkel, N. (1982) The herpes simplex virus amplicon: a new eucaryotic defective-virus cloning-amplifying vector. Cell 30, 305–310.
Spaete, R. R. and Frenkel, N. (1985) The herpes simplex virus amplicon: analyses of cis-acting replication functions. Proc. Natl. Acad. Sci. USA 82, 694–698.
Stow, N. D. and McMonagle, E. (1982) Propagation of foreign DNA sequences linked to a herpes simplex virus origin of replication, in Eucaryotic Viral Vectors (Gluzman, Y., ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 199–204.
Frenkel, N., Locker, H., Batterson, W. Hayward, G. S., and Roizman, B. (1976) Anatomy of herpes simplex virus DNA. VI. Defective DNA originates from the S component. J. Virol. 20(2), 527–531.
Geller, A. I. and Federoff, H. J. (1991) The use of HSV-1 vectors to introduce heterologous genes into neurons: implication for gene therapy, in Human Gene Transfer (Cohen-Haguenauer, O. and Boiron, M., eds.), Colloque INSERM/John Libbey Eurotext, Montrouge, France, pp. 63–73.
Geschwind, M. D., Kessler, J. A., Geller, A. I., and Federoff, H. J. (1994) Transfer of the nerve growth factor gene into cell lines and cultured neurons using a defective herpes simplex virus vector. Transfer of the NGF gene into cells by a HSV-1 vector. Mol. Brain Res. 24, 327–335.
Kaplitt, M. G., Leone, P., Samulski, R. J., et al. (1994) Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 8(Oct.), 148–154.
Lu, B. and Federoff, H. J. (1995) Herpes simplex virus type 1 amplicon vectors with glucocorticoid-inducible gene expression. Hum. Gene Ther. 6, 421–430.
Jin, B. K., Belloni, M., Conti, B., et al. (1996) Prolonged in vivo gene expression driven by a tyrosine hydroxylase promoter in a defective herpes simplex virus amplicon vector. Hum. Gene Ther. 7, 2015–2024.
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., and Wang, X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cyto-chrome c. Cell 86, 147–157.
Brooks, A. I., Muhkerjee, B., Panahian, N., Cory-Slechta, D., and Federoff, H. J. (1997) Nerve growth factor somatic mosaicism produced by herpes virus-directed expression of cre recombinase. Nat. Biotechnol. 15, 57–62.
Halterman, M. W., Miller, C. C., and Federoff, H. J. (1999) Hypoxia-induci-ble factor-1α mediates hypoxia-induced delayed neuronal death that involves p53. J. Neurosci. 19(16), 6818–6824.
During, M. J., Naegele, J. R., O’Malley, K. L., and Geller, A. I. (1994) Long-term behavioral recovery in Parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. Science 266, 1399–1403.
Harvey, D. M. and Caskey, C. T. (1998) Inducible control of gene expression: prospects for gene therapy. Curr. Opin. Chem. Biol. 2(4), 512–518.
Gossen, M. and Bujard, H. (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA 89 (12), 5547–5551.
Strathdee, C. A., McLeod. M. R., and Hall. J. R. (1999) Efficient control of tetracycline-responsive gene expression from an autoregulated bi-directional expression vector. Gene 229(1-2), 21–29.
Kerr, J. F., Wyllie. A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26(4), 239–257.
Michel, P. P., Lambeng, N., and Ruberg, M. (1999) Neuropharmacologic aspects of apoptosis: significance for neurodegenerative diseases. Clin. Neuro-pharmacol. 22 (3), 137–150.
Emerich, D. and Bartus, R. (1999) Intracellular events associated with cerebral ischemia, in Stroke Therapy: Basic, Preclinical, and Clinical Directions (Miller, L., ed.), Wiley-Liss, New York, pp. 195–218.
Sapolsky, R. M. and Steinberg, G. K. (1999) Gene therapy using viral vectors for acute neurologic insults. Neurology 53(9), 1922–1931.
Hatterman, M. W. and Federoff, H. J. (1999) Hif-1a and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia. Exp. Neurol. 159, 65–72.
Siesjo, B. K. (1981) Cell damage in the brain. J. Cereb. Blood Flow Metab. 1, 155–185.
Koroshetz, W. J. and Moskowitz, M. A. (1996) Emerging treatments for stroke in humans. TiPS 17, 227–233.
Collaco-Moraes, Y., Aspey, B. S., de Belleroche, J. S., and Harrison, M. J. G. (1994) Focal ischemia causes an extensive induction of immediate early genes that are sensitive to MK-801. Stroke 25, 1855–1861.
Gillardon, F., Lenz, C., Waschke, K. F., et al. (1996) Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ische-mic cell damage following middle cerebral artery occlusion in rats. Mol. Brain Res. 40, 254–260.
Kogure, K. and Kato, H. (1993) Altered gene expression in cerebral ischemia. Stroke 24(12), 2121–2127.
Xiang, H., Kinoshita, Y., Knudson, C. M., Korsmeyer, S. J., Schwartzkroin, P. A., and Morrison, R. S. (1998) Bax involvement in p53-mediated neuronal cell death. J. Neurosci. 18(4), 1363–1373.
Bakhshi, A., Jensen, J. P., Goldman, P., et al. (1985) Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 41 (3), 899–906.
Cleary, M. L. and Sklar, J. (1985) Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a break-point-cluster region near a transcriptionally active locus on chromosome 18. Proc. Natl. Acad. Sci. USA 82(21), 7439–7443.
Hockenbery, D., Nunez, G., Milliman, C., Schreiber, R. D., and Korsmeyer, S. J. (1990) Bcl-2 is an inner mitochondrial membrane protein blocks programmed cell death. Nature 348, 334–336.
Krajewski, S., Tanaka, S., Takayama, S., Schibler, M. J., Fenton, W., and Reed, J. C. (1993) Investigation of the subcellular distribution of the bcl-2oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res. 53 (19), 4701–4714.
Merry, D. E. and Korsmeyer, S. J. (1997) Bcl-2 gene family in the nervous system. Annu. Rev. Neurosci. 20, 245–267.
Monaghan, P., Robertson, D., Amos, T. A. S., Dyer, M. J. S., Mason, D. Y., and Greaves, M. F. (1992) Ultrastructural localization of bcl-2 protein. J. His-tochem. Cytochem. 40(12), 1819–1825.
Tsujimoto, Y., Gorham, J., Cossman, J., Jaffe, E., and Croce, C. M. (1985) The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 229, 1390–1393.
Reed, J. C. (1997) Double identity for proteins of the Bcl-2 family. Nature 387, 773–776.
Allsopp, T. E., Wyatt, S., Paterson, H. F., and Davies, A. M. (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73, 295–307.
Asahi, M., Hoshimaru, M., Uemura, Y., et al. (1997) Expression of inter-leukin-1β converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery. J. Cereb. Blood Flow Metabol. 17, 11–18.
Behl, C., Hovey, L. III, Krajewski, S., Schubert, D., and Reed, J. C. (1993) Bcl-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein. Biochem. Biophys. Res. Commun. 197(2), 949–956.
Chen, J., Graham, S. H., Nakayama, M., et al. (1997) Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain following global ischemia. J. Cereb. Blood Flow Metabol. 17, 2–10.
Honkaniemi, J., Massa, S. M., Breckinridge, M., and Sharp, F. R. (1996) Global ischemia induces apoptosis-associated genes in hippocampus. Mol. Brain Res. 42, 79–88.
Kane, D. J., Sarafian, T. A., Anton, R., et al. (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277.
Linnik, M. D., Zahos, P., Geschwind, M. S., and Federoff, H. J. (1995) Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia. Stroke 26, 1670–1675.
Martinou, J.-C., Dubois-Dauphin, M., Staple, J. K., et al. (1994) Overexpres-sion of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030.
Zhong, L.-T., Sarafian, T., Kane, D. J., et al. (1993) Bcl-2 inhibits death of central neural cells induced by multiple agents. Proc. Natl. Acad. Sci. USA 90, 4533–4537.
McDonnell, T. J., Deane, N., Platt, F. M., et al. (1989) Bcl-2-immunoglobu-lin transgenic mice demonstrate extended B cell survival and follicular lym-phoproliferation. Cell 57, 79–88
Vaux, D. L., Weissman, I. L., and Kim, S. K. (1992) Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science 258, 1955–1957.
Eizenberg, O., Faber-Elman, A., Gottlieb, E., Oren, M., Rotter, V., and Schwartz, M. (1996) p53 plays a regulatory role in differentiation and apop-tosis of central nervous system-associated cells. Mol. Cell Biol. 16(9), 5178–5185.
Jordan, J., Galindo, M. F., Prehn, J. H., et al. (1997) p53 expression induces apoptosis in hippocampal pyramidal neuron cultures. J. Neurosci. 17(4), 1397–1405.
Shinoura, N., Satou, R., Yoshida, Y., Asai, A., Kirino, T., and Hamada, H. (2000) Adenovirus-mediated transfer of Bcl-X(L) protects neuronal cells from Bax-induced apoptosis. Exp. Cell Res. 254(2), 221–231.
Slack, R. S., Belliveau, D. J., Rosenberg, M., et al. (1996) Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in post-mitotic neurons. J. Cell Biol. 135(4), 1085–1096.
Antonawich, F. J., Federoff, H. J., and Davis, J. N. (1999) BCL-2 transduc-tion, using a herpes simplex virus amplicon, protects hippocampal neurons from transient global ischemia. Exp. Neurol. 156(1), 130–137.
Tsai, T. H., Chen, S. L., Chiang, Y. H., et al. (2000) Recombinant adeno-associated virus vector expressing glial cell line-derived neurotrophic factor reduces ischemia-induced damage. Exp. Neurol. 166(2), 266–275.
Goldberg, M. A., Dunning, S. P., and Bunn, H. F. (1988) Regulation of the ery-thropoietin gene: evidence that the oxygen sensor is a heme protein. Science 242 (4884), 1412–1415.
Srinivas, V., Zhu, X., Salceda, S., Nakamura, R., and Caro, J. (1998) Hypoxia-inducible factor 1alpha (HIF-1alpha) is a non-heme iron protein. Implications for oxygen sensing. J. Biol. Chem. 273(29), 18,019–18,022.
Blanchard, K. L., Acquaviva, A. M., Galson, D. L., and Bunn, H. F. (1992) Hypoxic induction of the human erythropoietin gene: cooperation between the promoter and enhancer, each of which contains steroid receptor response elements. Mol. Cell Biol. 12(12), 5373–5385.
Guillemin, K. and Krasnow, M. A. (1997) The hypoxic response: huffing and HIFing. Cell 89(1), 9–12.
Halterman, M. and Federoff, H. (1999) HIF-1α cooperates with p53 to promote hypoxia induced neuronal death, in Keystone Symposia-Apoptosis and Programmed Cell Death, Keystone Symposia, Breckenridge, CO, p. 53.
Van de Water, T. R., Staecker, H., Halterman, M. W., and Federoff, H. J. (1999) Gene therapy in the inner ear. Mechanisms and clinical implications. Ann. N.Y. Acad. Sci. 884, 345–360.
Ard, M. D., Morest, D. K., and Hauger, S. H. (1985) Trophic interactions between the cochleovestibular ganglion of the chick embryo and its synap-tic targets in culture. Neuroscience 16(1), 151–170.
Koitchev, K., Aran, J. M., Ivanov, E., and Cazals, Y. (1986) Progressive degeneration in the cochlear nucleus after chemical destruction of the cochlea. Acta Otolaryngol. 102(1-2), 31–39.
Pfingst, B. E. and Sutton, D. (1983) Relation of cochlear implant function to histopathology in monkeys. Ann. N.Y. Acad. Sci. 405, 224–239.
Spoendlin, H. (1971) Primary structural changes in the organ of Corti after acoustic overstimulation. Acta Otolaryngol. 71(2), 166–176.
Webster, M. and Webster. D. B. (1981) Spiral ganglion neuron loss following organ of Corti loss: a quantitative study. Brain Res. 212(1), 17–30.
Ylikoski, J., Wersall, J., and Bjorkroth, B. (1974) Degeneration of neural elements in the cochlea of the guinea-pig after damage to the organ of corti by ototoxic antibiotics. Acta Otolaryngol. Suppl. 326, 23–41.
Zhou, X. N. and Van de Water, T. R. (1987) The effect of target tissues on survival and differentiation of mammalian statoacoustic ganglion neurons in organ culture. Acta Otolaryngol. 104(1-2), 90–98.
Lefebvre, P. P., Van de Water, T. R., Staecker, H., et al. (1992) Nerve growth factor stimulates neurite regeneration but not survival of adult auditory neurons in vitro. Acta Otolaryngol. 112(2), 288–293.
Ylikoski, J., Pirvola, U., and Happola, O. (1993) Characterization of the vestibular and spiral ganglion cell somata of the rat by distribution of neu-rofilament proteins. Acta Otolaryngol. Suppl. 503, 121–126.
Ernfors, P., Lee, K. F., and Jaenisch, R. (1994) Target derived and putative local actions of neurotrophins in the peripheral nervous system. Prog. Brain Res. 103, 43–54.
Schecterson, L. C. and Bothwell, M. (1994) Neurotrophin and neurotro-phin receptor mRNA expression in developing inner ear. Hear. Res. 73 (1), 92–100.
Chen, X., Frisina, R. D., Bowers, W. J., Frisina, D. R., and Federoff, H. J. (2001) Hsv amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage. Mol. Ther. 3(6), 958–963.
Hartshorn, D. O., Miller, J. M., and Altschuler, R. A. (1991) Protective effect of electrical stimulation in the deafened guinea pig cochlea. Otolaryngol. Head Neck Surg. 104 (3), 311–319.
Michelson, R. P. and Schindler, R. A. (1983) Surgical approach for insertion of multichannel electrodes into the scala tympani. Ann. N.Y. Acad. Sci. 405, 343–347.
Staecker, H., Gabaizadeh, R., Federoff, H., and Van De Water, T. R. (1998) Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss. Otolaryngol. Head Neck Surg. 119 (1), 7–13.
Carenza, L., Villani, C., Framarino dei Malatesta, M. L., et al. (1986) Peripheral neuropathy and ototoxicity of dichlorodiamineplatinum: instrumental evaluation. Preliminary results. Gynecol. Oncol. 25(2), 244–249.
Fleischman, R. W., Stadnicki, S. W., Ethier, M. F., and Schaeppi, U. (1975) Ototoxicity of cis-dichlorodiammine platinum (II) in the guinea pig. Toxicol. Appl. Pharmacol. 33(2), 320–332.
Nakai, Y., Konishi, K., Chang, K. C., et al. (1982) Ototoxicity of the anti-cancer drug cisplatin. An experimental study. Acta Otolaryngol. 93(3-4), 227–232.
Rybak, L. P. (1981) Cis-platinum associated hearing loss. J. Laryngol. Otol. 95(7), 745–747.
Cavaletti, G. and Tredici, G. (1996) Evaluation of cisplatin neuroprotection by NT-3. Ann. Neurol. 39(6), 827.
Zheng, J. L., Stewart, R. R., and Gao, W. Q. (1995) Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity. J. Neurosci. 15 (7 Pt 2), 5079–5087.
Han, J. J., Mhatre, A. N., Wareing, M., et al. (1999) Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector. Hum. Gene Ther. 10 (11), 1867–1873.
Stover, T., Yagi, M., and Raphael, Y. (1999) Cochlear gene transfer: round window versus cochleostomy inoculation. Hear. Res. 136(1-2), 124–130.
Bowers, W. J., Howard, D. F., Brooks, A. I., Halterman, M. W., and Federoff, H. J. (2001) Expression of vhs and VP16 during HSV-1 helper virus-free amplicon packaging enhances titers. Gene Ther. 8(2), 111–120.
Bowers, W. J., Howard, D. F., and Federoff, H. J. (2000) Discordance between expression and genome transfer titering of HSV amplicon vectors: recommendation for standardized enumeration. Mol. Ther. 1(3), 294–299.
Stavropoulos, T. A. and Strathdee, C. A. (1998) An enhanced packaging system for helper-dependent herpes simplex virus vectors. J. Virol. 72(9), 7137–7143.
Sena-Esteves, M., Saeki, Y., Fraefel, C., and Breakefield, X. O. (2000) HSV-1 amplicon vectors-simplicity and versatility. Mol. Ther. 2(1), 9–15.
Saeki, Y., Fraefel, C., Ichikawa, T., Breakefield, X. O., and Chiocca, E. A. (2001) Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. Mol. Ther. 3(4), 591–601.
Brooks, A. I., Cory-Slechta, D. A., Bowers, W. J., Murg, S. L., and Federoff, H. J. (2000) Enhanced learning in mice parallels vector-mediated nerve growth factor expression in hippocampus. Hum. Gene Ther. 11(17), 2341–2352.
Brooks, A. I., Cory-Slechta, D. A., and Federoff, H. J. (2000) Gene-experience interaction alters the cholinergic septohippocampal pathway of mice. Proc. Natl. Acad. Sci. USA 97 (24), 13,378–13,383.
Brooks, A. I., Halterman, M. W., Chadwick, C.A., et al. (1998) Reproducible and efficient murine CNS gene delivery using a microprocessor-controlled injector. J. Neurosci. Meth. 80(2), 137–147.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Maguire-Zeiss, K.A., Bowers, W.J., Federoff, H.J. (2002). HSV Amplicon Vectors in Neuronal Apoptosis Studies. In: LeBlanc, A.C. (eds) Apoptosis Techniques and Protocols. Neuromethods, vol 37. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-188-4:061
Download citation
DOI: https://doi.org/10.1385/1-59259-188-4:061
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-1-58829-012-0
Online ISBN: 978-1-59259-188-6
eBook Packages: Springer Protocols