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Gene Therapy Protocols pp 79–102Cite as

Development of Replication-Defective Herpes Simplex Virus Vectors

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Part of the book series: Methods in Molecular Medicine ((MIMM,volume 7))

Abstract

Numerous diseases of the nervous system result from single gene or multifactorial gene defects such as cancer, immune pathological disorders, metabolic diseases, and common neurodegenerative syndromes (Parkinson’s and Alzheimer’s diseases). A greater understanding of the molecular, biochemical, and genetic factors involved in the progression of a specific disease state has led to the development of genetic therapies using direct gene transfer to ameliorate the disease condition or correct a genetic defect in situ. Standard gene therapeutic approaches employing retroviruses have not proven feasible for treating disorders of the central nervous system (CNS) since these vectors require dividing cells for integration and expression of the transgene, whereas CNS neurons are postmitotic, terminally differentiated cells. Thus, methods for delivery and expression of therapeutic gene products to treat CNS disease will require new delivery strategies and vehicles including the development of novel vectors for direct gene transfer. These vectors should: efficiently deliver the therapeutic gene(s) to a sufficient number of nondividing neurons; persist long-term in a nonintegrated state within the nerve cell nucleus without disturbing host cell functions; and be able to regulate therapeutic gene expression for diseases that may either require high-level transient transgene expression or continuous low level synthesis of the therapeutic product.

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References

  1. Dressler, G. R., Rock, D. L., and Fraser, N W. (1987) Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo J. Gen Virol 68, 1761–1765.

    Article  CAS  Google Scholar 

  2. Mellerick, D. M. and Fraser, N. (1987) Physical state of the latent herpes simplex virus genome in a mouse model system: evidence suggesting an episomal state Virology 158, 265–275.

    Article  CAS  Google Scholar 

  3. Rock, D. L. and Fraser, N. W (1985) Latent herpes simplex virus type 1 DNA contains two copies of the virion joint region J Virol. 55, 849–852.

    Article  CAS  Google Scholar 

  4. Croen, K. D., Ostrove, J. M., Dragovic, L. J., Smialek, J. E., and Straus, S E. (1987) Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene “anti-sense” transcript by in situ hybridization. N. Engl. J Med 317, 1427-1432.

    Article  CAS  Google Scholar 

  5. Deatly, A. M., Spivack, J. G., Lavi, E., and Fraser, N. W. (1987) RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proc Natl Acad Sci USA 84, 3204–3208.

    Article  CAS  Google Scholar 

  6. Gordon, Y. J., Johnson, B., Romanowski, E., and Araullo-Cruz, T. (1988) RNA complementary to herpes virus type 1 ICPO demonstrated in neurons of human trigeminal ganglia. J. Virol. 62, 1832-1835.

    Article  CAS  Google Scholar 

  7. Rock, D. L., Nesburn, A. B., Ghiasi, H., Ong, J., Lewis, T. L., Lokensgard, J. R., and Wechsler, S. (1987) Detection of Iatency-related viral RNAs in trigeminal ganglia of rabbits infect with herpes simplex virus type 1.J. Virol. 61, 3820–3826.

    Article  CAS  Google Scholar 

  8. Spivack, J. G. and Fraser, N. W. (1987) Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J. Viral 61, 3841–3847.

    Article  CAS  Google Scholar 

  9. Stevens, J. G., Wagner, E. K, Devi-Rao, G. B., Cook, M. L., and Feldman, L. T. (1987) RNA complementary to a herpesviruses α gene mRNA is prominent in latently infected neurons. Science 255, 1056–1059.

    Article  Google Scholar 

  10. Fareed, M. U and Spivack, J. G. (1994) Two open reading frames (ORF1 and ORF2) within the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency. J. Virol. 68, 8071–8081.

    Article  CAS  Google Scholar 

  11. Hill, l. M., Sedarati, F., Javier, R. T., Wagner, E. K., and Stevens, J G. (1990) Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174, 117–125.

    Article  CAS  Google Scholar 

  12. Ho, D. Y. and Mocarski, E. S. (1989) Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc. Natl. Acad. Sci. USA 86, 7596–7600.

    Article  CAS  Google Scholar 

  13. Javier, R. T., Stevens, J G., Dissette, V B., and Wagner, E K (1988) A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state Virology 166, 254–257.

    Article  CAS  Google Scholar 

  14. Leib, D. A., Bogard, C. L., Kosz-Vnenchak, M., Hicks, K. A., Coen, D. M., Knipe, D M., and Schaffer, P A. (1989) A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent infection. J Virol 63, 2893–2900.

    Article  CAS  Google Scholar 

  15. Sedarati, F., Izumi, K. M, Wagner, E K., and Stevens, J. G (1989) Herpes simplex virus type 1 latency-associated transcript plays no role in establishment or maintenance of a latent infectron in murine sensory neurons. J. Virol 63, 4455–4458.

    Article  CAS  Google Scholar 

  16. Steiner, I., Spivack, J G., Lirette, R. P, Brown, S. M., MacLean, A. R, Subak-Sharpe, J., and Fraser, N W. (1989) Herpes simplex virus type 1 latency-assoclated transcripts are evidently not essential for latent infection. EMBO J 8, 505–511.

    Article  CAS  Google Scholar 

  17. Roizman, B and Sears, A. E. (1990)Herpes simplex viruses and then replication, in Field’s Virology, 2nd ed. (Fields B. N., Knipe, D. M, Chanock, R. M., Hirsch, M S, Melnick, J. L., and Roizman, B.,eds.), Raven, New York, pp 1795–1841.

    Google Scholar 

  18. Spear, P G. (1993) Membrane fusion induced by herpes simplex virus, in Viral Fuszon Mechanisms (Bentz, J, ed), CRC, Boca Raton, FL, pp 201–232.

    Google Scholar 

  19. Kwong, A. D. and Frenkel, N. (1987) Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proc Natl Acad. Sci. USA 84, 1926–1930.

    Article  CAS  Google Scholar 

  20. Kwong, A D., Kruper, J. A., and Frenkel, N. (1988) Herpes simplex virus virion host shutoff function J. Virol 62, 912–921.

    Article  CAS  Google Scholar 

  21. Oroskar, A. A. and Read, G. S. (1989) Control of mRNA stability by the virion host shutoff function of herpes simplex virus J. Virol. 63, 1897–1906.

    Article  CAS  Google Scholar 

  22. Read, G. S. and Frenkel, N. (1983) Herpes simplex virus mutants defective in the virion-associated shut off of host polypeptide synthesis and exhibiting abnormal synthesis of α (immediate early) viral polypeptides. J. Virol 46, 498–512.

    Article  CAS  Google Scholar 

  23. Ace, C I., McKee, T A., Ryan, M., Cameron, J M., and Preston, C M. (1989) Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. J. Virol 63, 2260–2269.

    Article  CAS  Google Scholar 

  24. Batterson, W. and Roizman, B. (1983) Characterization of the herpes simplex virion-associated factor responsible for the induction of α genes. J. Virol 46, 371–377.

    Article  CAS  Google Scholar 

  25. Campbell, M. E. M., Palfreyman, J. W., and Preston, C. M. (1984) Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J. Mol. Biol. 180, 1–19.

    Article  CAS  Google Scholar 

  26. Kristie, T. M. and Roizman, B. (1987) Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus type 1 α genes Proc Natl Acad Sci USA 84, 71–75.

    Article  CAS  Google Scholar 

  27. McKnight, J. L. C, Kristie, T. M., and Roizman, B. (1987) Binding of the virion protein mediating α gene induction in herpes simplex virus type 1-infected cells to its cis site requires cellular proteins. Proc. Natl. Acad sci USA 84, 7061–7065.

    Article  CAS  Google Scholar 

  28. Post, L. E., Mackem, S., and Roizman, B. (1981) Regulation of α genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with α gene promoters. Cell 24, 555–565.

    Article  CAS  Google Scholar 

  29. Newcomb, W. W and Brown, J. C. (1994) Induced extrusion of DNA from the capsid of herpes simplex virus type 1 J. Viral. 68, 443–450.

    Google Scholar 

  30. McGeoch, D. J., Dolan, A., Donald, S., and Rixon, F. J. (1985) Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J, Mol. Biol. 181, 1–13.

    Article  CAS  Google Scholar 

  31. McGeoch, D. J., Dolan, A., Donald, S., and Brauer, D. H. (1986) Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res 14, 1727–1744.

    Article  CAS  Google Scholar 

  32. McGeoch, D J., Dalrymple, M A., Davison, A. J., Dolan, A., Frame, M. C, McNab, D., Perry, L. J., Scott, J. E., and Taylor, P. (1988) The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1 J. Gen Virol. 69, 1531–1574.

    Article  CAS  Google Scholar 

  33. Roizman, B. and Sears, A. E. (1993) Herpes simplex virus and their replication, in The Human Herpesviruses (Roizman, B., Whitley, R. J., and Lopez, C., eds.), Raven, New York, pp. 11–68.

    Google Scholar 

  34. Honess, R. W. and Roizman, B. (1974) Regulation of herpes virus macromolecular synthesis. I. cascade regulation of the synthesis of three groups of viral proteins. J. Virol 14, 8–19.

    Article  CAS  Google Scholar 

  35. DeLuca, N. A., McCarthy, A. M., and Schaffer, P. A. (1985) Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J. Virol 56, 558–570.

    Article  CAS  Google Scholar 

  36. Dixon, R. A. F. and Schaffer, P. A. (1980) Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 Immediate early protein VP175 J. Virol. 36, 189–203.

    Article  CAS  Google Scholar 

  37. O’Hare, P. and Hayward, G. S. (1985) Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J. Virol. 56, 723–733.

    Article  Google Scholar 

  38. Preston, C. M. (1979) Abnormal properties of an immediate early polypeptide in cells infected with herpes simplex virus type 1 mutant tsK. J. Virol. 32, 357–369

    Article  CAS  Google Scholar 

  39. Sacks, W. R., Greene, C. C., Aschman, D. A., and Schaffer, P. A. (1985) Herpes simplex virus type 1ICP27 is an essential regulatory protein. J. Virol. 55, 796–805.

    Article  CAS  Google Scholar 

  40. Sacks, W. R. and Schaffer, P. A. (1987) Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICPO exhibit impaired growth in cell culture. J. Virol. 61, 829–839.

    Article  CAS  Google Scholar 

  41. Stow, N. D. and Stow, E. C. (1986) Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw 110. J. Gen. Virol. 67, 2571–2585.

    Article  CAS  Google Scholar 

  42. Watson, R. J. and Clements, J. B. (1980) A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature 285.329,330.

    Article  CAS  Google Scholar 

  43. Holland, L. E, Anderson, K. P., Shipman, C., and Wagner, E. K. (1980) Viral DNA synthesis is required for efficient expression of specific herpes simplex virus type 1 mRNA Virology 101, 10–24.

    Article  CAS  Google Scholar 

  44. Mavromara-Nazos, P. and Roizman, B. (1987) Activation of herpes simplex type 1 γ2 genes by viral DNA replication. Virology 161, 593–598.

    Article  CAS  Google Scholar 

  45. Cook, M. L. and Stevens, J. G. (1973) Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence of intra-axonal transport of infection. Infect. Immun 7, 272–288.

    Article  CAS  Google Scholar 

  46. Stevens, J. G (1989) Human herpesviruses: a consideration of the latent state. Microbial Rev. 53, 318–332.

    Article  CAS  Google Scholar 

  47. Deshmane, S L. and Fraser, N. W (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J. Virol 63, 943–947.

    Article  CAS  Google Scholar 

  48. Johnson, P. A., Miyanohara, A., Levine, F., Cahill, T., and Friedmann, T. (1992) Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1. J. Virol. 33, 272–285.

    Google Scholar 

  49. Leiden, J. M., Frenkel, N., and Rapp, F. (1980) Identification of herpes simplex virus DNA sequences present in six thymidine kinase-transformed mouse cell lines. J. Virol 33, 272–285.

    Article  CAS  Google Scholar 

  50. Samaniego, L., Webb, A., and DeLuca, N. (1995) Functional interaction between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4 J. Virol. 69, 5705–5715.

    Article  CAS  Google Scholar 

  51. Katan, M., Haigh, A., Verrijizer, C. B., van der Vliet, P. C. and O’Hare, P. (1990) Characterization of a cellular factor which interacts functionally with Oct-1 in the assembly of a multicomponent transcription complex. Nucleic Acids Res 18, 6871–6880.

    Article  CAS  Google Scholar 

  52. Kristie, T. M. and Sharp, P. A. (1993) Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by herpes simplex virus a-trans-induction factor (VP16). J. Biol Chem 268, 6525–6534.

    Article  CAS  Google Scholar 

  53. Xiao, P. and Capone, J. P. (1990) A cellular factor binds to the herpes simplex virus type 1 transactivator Vmw65 and is required for Vmw65-dependent protein-DNA complex assembly with Oct-1. Mol. Cell. Biol. 10, 4974–4977.

    CAS  Google Scholar 

  54. Wilson, A. C., LeMarco, K., Peterson, M. G., and Herr, W. (1993) The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein Cell 74, 115–125.

    Article  CAS  Google Scholar 

  55. Werstuck, G. H. and Capone, J. P. (1993) An unusual cellular factor potentiates protein-DNA complex assembly between Oct-1 and Vmw65 J. Biol Chem. 268, 1272–1278.

    Article  CAS  Google Scholar 

  56. Gerster, T and Roeder, R. G (1988) A herpesvirus trans-acting protein interacts with the transcription factor OTF-1 and other cellular proteins. Proc Natl. Acad. Sci USA 85, 6347–6351.

    Article  CAS  Google Scholar 

  57. O’Hare, P. and Goding, C. R. (1988) Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell 52, 435–445.

    Article  Google Scholar 

  58. Preston, C. M., Frame, M. C., and Campbell, M. E. M. (1988) A complex formed between cell components and an herpes simplex virus type 1 structural polypeptide binds to a viral immediate early gene regulatory DNA sequence Cell 52, 425–435.

    Article  CAS  Google Scholar 

  59. Stern, S., Tanaka, M., and Herr, W. (1989) The Oct-1 homeodomain directs formation of a multi-protein-DNA complex with the herpes simplex virus transactivator VP16 Nature 341, 624–630.

    Article  CAS  Google Scholar 

  60. Cai, W. Z and Schaffer, P. A. (1989) Herpes simplex virus type 1 ICPO plays a critical role in the de novo synthesis of infectious virus following transfection of viral DNA. J. Virol 63, 4579–4589.

    Article  CAS  Google Scholar 

  61. Everett, R. D (1987) The regulation of transcription of viral and cellular genes by herpesvirus immediate-early gene products. Anticancer Res 7, 589–604.

    CAS  Google Scholar 

  62. Gelman, I. H. and Silverstein, S. (1985) Identification of immediate-early genes from herpes simplex virus that transactivate the virus thymidine kinase gene. Proc Natl. Acad. Sci. USA 82, 5265–5269.

    Article  CAS  Google Scholar 

  63. O’Hare, P. and Hayward, G. S. (1985) Evidence for a direct role for both the 175,000 and 110,000-molecular-weight immediate-early protein of herpes simplex virus in transactivation of delayed-early promoters. J. Virol 53, 751–760.

    Article  Google Scholar 

  64. Cai, W and Schaffer, P. A. (1992) Herpes simplex virus type 1 ICPO regulates expression of immediate-early, early, and late genes in productively infected cells. J. Virol. 66, 2904–2915.

    Article  CAS  Google Scholar 

  65. Quinlan, M. P. and Knipe, D. M. (1985) Stimulation of expression of a herpes simplex virus DNA-binding protein by two viral factors. Mol. Cell Biol 5, 957–963.

    CAS  Google Scholar 

  66. Zhu, Z., Cai, W., and Schaffer, P. A. (1994) Cooperativity among herpes simplex virus type 1 immediate-early regulatory protems: ICP4 and ICP27 affect the intra-cellular localization of ICPO. J. Virol 68, 3027–3040

    Article  CAS  Google Scholar 

  67. Maul, G. G. and Everett, R. D. (1994) The nuclear localization of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICPO. J. Gen. Virol. 75, 1223–1233.

    Article  CAS  Google Scholar 

  68. Chen, J. and Silverstein, S. (1992) Herpes simplex viruses with mutations in the gene encoding ICPO are defective in gene expression. J. Virol 66, 2916–2927.

    Article  CAS  Google Scholar 

  69. Rice, S. A., Long, M. C., Lam, V., and Spencer, C. A. (1994) RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection. J. Viral. 68, 988–1001.

    Article  CAS  Google Scholar 

  70. Hill, A., Jugovic, P., and York, I. A. (1995) Herpes simplex virus turns off the TAP to evade host immunity. Nature 375, 411–415.

    Article  CAS  Google Scholar 

  71. York, I. A., Roo, C., Andrews, D. W., Riddell, S. R., Graham, F L., and Johnson, D. C. (1994) A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+T lymphocytes. Cell 77, 525–535.

    Article  CAS  Google Scholar 

  72. Johnson, P. A., Wang, M. J., and Friedman, T. (1994) Improved cell survival by the reduction of immediate-early gene expression in replication-defective mutants of herpes simplex virus type 1 but not by mutation of the virion host shutoff function. J. Virol. 68, 6347–6362.

    Article  CAS  Google Scholar 

  73. Desai, P., Ramakrishnan, R., Lin, Z. W., Osak, B, Glorioso, J C, and Levine, M (1993) The RR1 gene of herpes simplex virus type 1 is uniquely transactivated by ICPO during infection J. Virol 67, 6125–6135.

    Article  CAS  Google Scholar 

  74. Luo, J. H. and Aurelian, L. (1992) The transmembrane helical segment but not the invariant lysine is required for the kinase activity of the large subunit of herpes simplex virus type 2 ribonucleotide reductase J. Biol Chem 267, 9645–9653.

    Article  CAS  Google Scholar 

  75. McCarthy, A M., McMahan, L., and Schaffer, P. A. (1989) Herpes simplex virus type 1 ICP27 deletion mutants exhibit altered patterns of transcription and are DNA deficient. J. Virol 63, 18–27.

    Article  CAS  Google Scholar 

  76. Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol Biol 98, 503–517.

    Article  CAS  Google Scholar 

  77. Graham, F L. and van der Eb, A. J. (1973) A new technique for the assay of infectivity of human adenovirus 5 DNA Virology 52, 456–467

    Article  CAS  Google Scholar 

  78. Shapira, M, Homa, F. L., Glorioso, J C., and Levine, M. (1987) Regulation of the herpes simplex virus type 1 late (γ2) glycoprotein C gene sequences between base pairs −34 to+29 control transient expression and responsiveness to transactivation by the products of immediate early (α) 4 and 0 genes. Nucleic Acids Res 15, 3097–3111.

    Article  CAS  Google Scholar 

  79. White, B. A. and Bancroft, F C. (1982) Cytoplasmic dot hybridization J. Biol Chem. 257, 8569–8572.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    David Krisky, Peggy Marconi, William F. Goins & Joseph C. Glorioso

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  1. David Krisky
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  2. Peggy Marconi
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  3. William F. Goins
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  4. Joseph C. Glorioso
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Editors and Affiliations

  1. University of Pittsburgh, PA, USA

    Paul D. Robbins

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Krisky, D., Marconi, P., Goins, W.F., Glorioso, J.C. (1997). Development of Replication-Defective Herpes Simplex Virus Vectors. In: Robbins, P.D. (eds) Gene Therapy Protocols. Methods in Molecular Medicine, vol 7. Humana, Totowa, NJ. https://doi.org/10.1385/0-89603-484-4:79

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  • DOI: https://doi.org/10.1385/0-89603-484-4:79

  • Publisher Name: Humana, Totowa, NJ

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