Herpesvirus Target Considerations for the Design of Antiviral Agents

  • Fred Rapp
  • Brian Wigdahl
Part of the NATO ASI Series book series (NSSA, volume 73)


The herpesviruses, herpes simplex virus (HSV) type 1 (HSV-1), HSV type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) can cause mild to severe diseases in humans.12 In addition to causing clinically apparent disease due to lytic virus replication, this group of viruses has been shown to be harbored in the human population in persistent and latent forms.3–6 Furthermore, several members have also been implicated in the etiology of certain human neoplasias.7,8 The herpesviruses contain a double-stranded DNA genome enclosed in an icosahedral capsid structure surrounded by a lipid envelope, and replicate virus DNA in the cell nucleus. Although the herpesviruses have several biological characteristics in common, the individual viruses differ in multiple parameters. A partial list is shown in Table 1.


Herpes Simplex Virus Type Thymidine Kinase Trigeminal Ganglion Human Herpesvirus Herpes Simplex Virus Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. J. Nahmías, W. R. Dowdle, and R. F. Schinazi, “The Human Herpesviruses: An Interdisciplinary Perspective,” Elsevier, New York (1981).Google Scholar
  2. 2.
    B. Roizman, “The Herpesviruses,” Vol. 2, Plenum Press, New York (1983).CrossRefGoogle Scholar
  3. 3.
    J. R. Baringer, Herpes simplex virus infections of the nervous system, in: “Handbook of Clinical Neurology: Infections of the Nervous System,” Vol. 34, Part II,“ P. J. Vinken and G. W. Bruyn, eds., North-Holland, New York (1978).Google Scholar
  4. 4.
    J. G. Stevens, Herpetic latency and reactivation, in: “Oncogenic Herpesviruses,” Vol. II, F. Rapp, ed., CRC Press, Boca Raton, Florida (1980).Google Scholar
  5. 5.
    R. J. Klein, The pathogenesis of acute, latent, and recurrent herpes simplex virus infections, Arch. Virol. 72: 143 (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Wildy, H. J. Field, and A. A. Nash, Classical herpes latency revisited, in: “Virus Persistence Symposium,” B. W. J. Mahy, A. C. Minson and G. K. Dardy, eds., Cambridge University Press, Cambridge (1982).Google Scholar
  7. 7.
    D. M. Knipe, Cell growth transformation by herpes simplex virus, Prog. Med. Virol. 28: 114 (1982).PubMedGoogle Scholar
  8. 8.
    F. Rapp, Viral carcinogenesis, in: “Aspects of Cell Regulation, International Review of Cytology,” J. F. Danielli, ed., Academic Press, Inc., New York (1983).Google Scholar
  9. 9.
    H. E. Kaufman and C. Heidelberger, Therapeutic antiviral action of 5-trifluoromethyl-2’-deoxyuridine in herpes simplex keratitis, Science 145: 585 (1964).PubMedCrossRefGoogle Scholar
  10. 10.
    H. E. Kaufman, Clinical cure of herpes simplex keratitis by 5-iodo-2’-deoxyuridine, Proc. Soc. Exp. Biol. Med. 109: 251 (1962).PubMedGoogle Scholar
  11. 11.
    W. H. Prusoff and B. Goz, Potential mechanisms of action of antiviral agents, Fed. Proc. 32: 1679 (1973).Google Scholar
  12. 12.
    W. E. G. Müller, Mechanisms of action and pharmacology: chemical agents, in: “Antiviral Agents and Viral Diseases of Man,” G. J. Galasso, T. C. Merigan and R. A., Buchanan, eds., Raven Press, New York (1979).Google Scholar
  13. 13.
    W. H. Prusoff and D. C. Ward, Commentary: nucleoside analogs with antiviral potency, Biochem. Pharmacol. 25: 1233 (1976).PubMedCrossRefGoogle Scholar
  14. 14.
    D. J. Bauer, “The Specific Treatment of Virus Diseases,” University Park Press, Baltimore (1977).Google Scholar
  15. 15.
    B. Roizman and D. Furlong, The replication of herpes-viruses, in: “Comprehensive Virology,” Vol. 3, H. FraenkelConrat and R. R. Wagner, eds., Plenum Press, New York (1974).Google Scholar
  16. 16.
    P. Spear and B. Roizman, Herpes simplex viruses, in: “DNA Tumor Viruses,” J. Tooze, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1980).Google Scholar
  17. 17.
    E. D. Kieff, S. L. Bachenheimer, and B. Roizman, Size, composition and structure of the DNA of subtypes 1 and 2 herpes simplex virus, J. Virol. 8: 125 (1971).PubMedGoogle Scholar
  18. 18.
    B. Roizman, The structure and isomerization of herpes simplex virus genomes, Cell 16: 481 (1979).PubMedCrossRefGoogle Scholar
  19. 19.
    E. D. Kieff, B. Hoyer, S. L. Bachenheimer, and B. Roizman, Genetic relatedness of type 1 and type 2 herpes simplex viruses, J. Virol. 9: 738 (1972).PubMedGoogle Scholar
  20. 20.
    P. Sheldrick and N. Berthelot, Inverted repetitions in the chromosome of herpes simplex virus, Cold Spring Harbor Symp. Quant. Biol. 39: 667 (1975).CrossRefGoogle Scholar
  21. 21.
    S. Wadsworth, R. J. Jacob, and B. Roizman, Anatomy of herpes virus DNA. II. Size, composition and arrangement of inverted terminal repetitions, J. Virol. 15: 1487 (1975).PubMedGoogle Scholar
  22. 22.
    G. S. Hayward, R. J. Jacob, S. C. Wadsworth, and B. Roizman, Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short segments, Proc. Natl. Acad. Sci. USA 72: 4243 (1975).PubMedCrossRefGoogle Scholar
  23. 23.
    H. Delius and J. B. Clements, A partial denaturation map of herpes simplex virus type 1 DNA: evidence for inversions of the unique DNA regions, J. Gen. Virol. 33: 125 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    R. W. Honess and B. Roizman, Proteins specified by herpes simplex virus. XI. Identification and relative molar rates of synthesis of structural and non-structural herpes-virus polypeptides in the infected cell, J. Virol. 12: 1346 (1973).Google Scholar
  25. 25.
    K. L. Powell and R. J. Courtney, Polypeptides synthesized in herpes simplex virus type 2-infected HEp-2 cells, Virology 66: 217 (1975).PubMedCrossRefGoogle Scholar
  26. 26.
    R. W. Honess and B. Roizman, Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins, J. Virol. 14: 8 (1974).PubMedGoogle Scholar
  27. 27.
    S. Mackem and B. Roizman, Regulation of herpesvirus macro-molecular synthesis: Transcrip’tíon-initiation sites and domains of a genes, Proc. Natl. Acad. Sci. USA 77: 7122 (1980).PubMedCrossRefGoogle Scholar
  28. 28.
    K. W. Wilcox, A. Kohn, E. Sklyanskay, and B. Roizman, Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA, J. Virol. 33: 167 (1980).PubMedGoogle Scholar
  29. 29.
    B. Roizman and P. R. Roane, The multiplication of herpes simplex virus. II. The relation between protein synthesis and the duplication of viral DNA in infected HEp-2 cells, Virology 22: 262 (1964).PubMedCrossRefGoogle Scholar
  30. 30.
    R. J. Sydiskis and B. Roizman, The disaggregation of host polyribosomes in productive and abortive infection with herpes simplex virus, Virology 32: 678 (1967).PubMedCrossRefGoogle Scholar
  31. 31.
    E. K. Wagner and B. Roizman, RNA synthesis in cells infected with herpes simplex virus. I. The patterns of RNA synthesis in productively infected cells. J. Virol. 4: 36 (1969).PubMedGoogle Scholar
  32. 32.
    M. L. Fenwick and M. J. Walker, Suppression of the synthesis of cellular macromolecules by herpes simplex virus, J. Gen. Virol. 41: 37 (1978).PubMedCrossRefGoogle Scholar
  33. 33.
    B. Roizman, M. Kozak, R. W. Honess, and G. Hayward, Regulation of herpes virus macromolecular synthesis: evidence for multilevel regulation of herpes simplex 1 RNA and protein synthesis, Cold Spring Harbor Symp. Quant. Biol. 39: 687 (1975).CrossRefGoogle Scholar
  34. 34.
    E. S. Huang, Human cytomegalovirus. III. Virus-induced DNA polymerase, J. Virol. 16: 298 (1975).PubMedGoogle Scholar
  35. 35.
    S. C. St. Jeor, T. B. Albrecht, F. D. Funk, and F. Rapp, Stimulation of cellular DNA synthesis by human cytomegalovírus, J. Vírol. 13: 353 (1974).PubMedGoogle Scholar
  36. 36.
    S. Tanaka, T. Furukawa, and S. A. Plotkin, Human cytomegalovirus stimulates host cell RNA synthesis, J. Virol. 15: 297 (1975).PubMedGoogle Scholar
  37. 37.
    M. F. Stinski, Synthesis of protein and glycoproteíns in cells infected with human cytomegalovirus, J. Virol. 23: 751 (1977).PubMedGoogle Scholar
  38. 38.
    K. Hirai and Y. Watanabe, Induction of a-type DNA polymerases in human cytomegalovirus-infected WI-38 cells, Biochím. Biophys. Acta 447: 328 (1976).Google Scholar
  39. 39.
    V. Zavada, V. Erban, D. Resacova, and V. Vonka, Thymidine kinase in cytomegalovirus infected cells, Arch. Virol. 52: 333 (1976).PubMedCrossRefGoogle Scholar
  40. 40.
    R. L. Miller, J. P. Iltis, and F. Rapp, Differential effect of arabinofuranosylthymine on the replication of human herpesviruses, J. Virol. 23: 679 (1977).PubMedGoogle Scholar
  41. 41.
    H. C. Isom, Stimulation of orníthine decarboxylase by human cytomegalovírus, J. Gen. Virol. 42: 265 (1979).PubMedCrossRefGoogle Scholar
  42. 42.
    J. A. Zaia, Clinical spectrum of varicella-zoster virus infection, in: “The Human Herpesviruses: An Interdisciplinary Perspective,” A. J. Nahmias, W. R. Dowdle, and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  43. 43.
    T. H. Weller, Clinical spectrum of cytomegalovirus infection, in: “The Human Herpesviruses: An Interdisciplinary Perspective,” A. J. Nahmias, W. R. Dowdle and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  44. 44.
    J. S. Pagano and J. G. Nedrud, Latency of the Epstein-Barr virus and cytomegalovirus, in: “The Human Herpesviruses: An Interdisciplinary Perspective,” A. J. Nahmías, W. R. Dowdle and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  45. 45.
    G. Klein, EBV-persistence in human lymphoid and carcinoma cells, in: “Persistant Viruses,” J. G. Stevens, G. J. Todaro, and C. F. Fox, eds., Academic Press, New York (1978).Google Scholar
  46. 46.
    M. Nonoyama and J. S. Pagano, Separation of Epstein-Barr virus DNA from large chromosomal DNA in non-virus producing cells, Nature (New Biol.) 238: 169 (1972).CrossRefGoogle Scholar
  47. 47.
    A. Adams, T. Lindahl, and G. Klein, Linear association between cellular DNA and Epstein-Barr virus DNA in a human lymphoblastoíd cell line, Proc. Natl. Acad. Sci. USA 70: 2888 (1973).PubMedCrossRefGoogle Scholar
  48. 48.
    P. Gerber, Activation of Epstein-Barr virus by 5-bromodeoxyuridine in virus-free human cells, Proc. Natl. Acad. Scí. USA 69: 83 (1972).PubMedCrossRefGoogle Scholar
  49. 49.
    A. Adams, G. Bjursell, C. Kaschka-Dierich, and T. Lindahl, Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin, J. Virol. 22: 373 (1977).PubMedGoogle Scholar
  50. 50.
    M. Anderson and T. Lindahl, Epstein-Barr virus DNA in human lymphoid cell lines: in vitro conversion, Virology 73: 96 (1976).CrossRefGoogle Scholar
  51. 51.
    S. D. Hayward and E. D. Kieff, Epstein-Barr virus-specific RNA. I. Analysis of viral RNA in cellular extracts and in the polyribosomal fraction of permissive and nonpermissive lymphoblastoid cell lines, J. Virol. 18: 518 (1976).PubMedGoogle Scholar
  52. 52.
    T. Orellana and E. Kieff, Epstein-Barr virus-specific RNA. II. Analysis of polyadenylated viral RNA in restríngent, abortive, and productive infections, J. Virol. 22: 321 (1977).PubMedGoogle Scholar
  53. 53.
    B. Hampar, A. Tanaka, M. Nonoyama, and J. G. Derge, Replication of the resident repressed Epstein-Barr virus genome during early S phase (S-1 period) of nonproducer Raji cells, Proc. Natl. Acad. Sci. USA 71: 631 (1974).PubMedCrossRefGoogle Scholar
  54. 54.
    A. J. Nahmías, J. Dannenbarger, C. Wickliffe, and J. Muther, Clinical aspects of infection with herpes simplex viruses 1 and 2, in: “The Human Herpesviruses: An Interdisciplinary Perspective,” A. J. Nahmias, W. R. Dowdle and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  55. 55.
    M. A. Walz, H. Yamamoto, and A. L. Notkins, Immunological response restricts number of cells in sensory ganglia infected with herpes simplex virus, Nature 264: 554 (1976).PubMedCrossRefGoogle Scholar
  56. 56.
    J. G. Stevens, Latent herpes simplex virus and the nervous system, Curr. Top. Microbiol. Immunol. 70: 31 (1975).PubMedCrossRefGoogle Scholar
  57. 57.
    A. Puga, J. D. Rosenthal, H. Openshaw, and A. L. Notkins, Herpes simplex virus DNA and mRNA sequences in acutely and chronically infected trigeminal ganglia of mice, Virology 89: 102 (1978).PubMedCrossRefGoogle Scholar
  58. 58.
    D. A. Galloway, C. Fenoglio, M. Shevchuck, and J. K. McDougall, Detection of herpes simplex RNA in human sensory ganglia, Virology 95: 265 (1979).PubMedCrossRefGoogle Scholar
  59. 59.
    D. A. Galloway, C. M. Fenoglio, and J. K. McDougall, Limited transcription of the herpes simplex virus genome when latent in human sensory ganglia, J. Virol. 41: 686 (1982).PubMedGoogle Scholar
  60. 60.
    R. B. Tenser, R. L. Miller, and F. Rapp, Trigeminal ganglion infection by thymidine kínase-negative mutants of herpes simplex virus, Science 205: 915 (1979).PubMedCrossRefGoogle Scholar
  61. 61.
    B. Fong and M. Scriba, Use of [1251] deoxycytidine to detect herpes simplex virus-specific thymidine kinase in tissues of latently infected guinea pigs, J. Virol. 34: 644 (1980).PubMedGoogle Scholar
  62. 62.
    M. T. Green, R. J. Courtney, and E. C. Dunkel, Detection of an immediate early herpes simplex virus type 1 polypeptide in trigeminal ganglia from latently infected animals, Infect. Immun. 34: 987 (1981).PubMedGoogle Scholar
  63. 63.
    K. L. Powell and D. J. M. Purífoy, DNA-binding proteins of cells infected by herpes simplex virus types 1 and 2, Intervírology 7: 225 (1976).PubMedGoogle Scholar
  64. 64.
    R. A. F. Dixon and P. A. Schaffer, Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP 175, J. Vírol. 36: 189 (1980).PubMedGoogle Scholar
  65. 65.
    K. W. Lofgren, J. G. Stevens, H. S. Marsden, and J. H. Subak-Sharpe, Temperature-sensitive mutants of herpes simplex virus differ in the capacity to establish latent infection in mice, Virology 76: 440 (1977).PubMedCrossRefGoogle Scholar
  66. 66.
    J. C. Gerdes, H. S. Marsden, M. L. Cook, and J. G. Stevens, Acute infection of differentiated neuroblastoma cells by latency-positive and latency-negative herpes simplex virus is mutants, Virology 94: 430 (1979).PubMedCrossRefGoogle Scholar
  67. 67.
    Y. Sokawa, T. Ando, and Y. Ishíhara, Induction of 2’,5’oligoadenylate synthetase and interferon in mouse trigeminal ganglia infected with herpes simplex virus, Infect. Immun. 28: 719 (1980).Google Scholar
  68. 68.
    D. L. Lodmell, A. Niwa, K. Hayashi, and A. L. Notkins, Prevention of cell to cell spread of herpes simplex virus by leukocytes, J. Exp. Med. 137: 706 (1973).PubMedCrossRefGoogle Scholar
  69. 69.
    J. G. Stevens and M. L. Cook, Maintenance of latent herpetic infection: an apparent role for antiviral IgG, J. Immunol. 113: 1685 (1974).PubMedGoogle Scholar
  70. 70.
    D. L. Rock and N. W. Fraser, Detection of HSV-1 genome in central nervous system of latently infected mice, Nature (London) 30: 523 (1983).CrossRefGoogle Scholar
  71. 71.
    N. W. Fraser, W. C. Lawrence, Z. Wroblewska, D. H. Gilden, and H. Koprowski, Herpes simplex type 1 DNA in human brain tissue, Proc. Natl. Acad. Sci. USA 78: 6461 (1981).PubMedCrossRefGoogle Scholar
  72. 72.
    M. Levine, A. L. Goldin, and J. C. Glorioso, Persistence of herpes simplex virus genes in cells of neuronal origin, J. Virol. 35: 203 (1980).PubMedGoogle Scholar
  73. 73.
    H. Youssoufian, S. M. Hammer, M. S. Hirsch, and C. Mulder, Methylation of the viral genome in an in vitro model of herpes simplex virus latency, Proc. Natl. Acad. Sci. USA 79: 2207 (1982).PubMedCrossRefGoogle Scholar
  74. 74.
    R. W. Price, R. Rubenstein, and A. Khan, Herpes simplex virus infection of isolated autonomic neurons in culture: viral replication and spread in a neuronal network, Arch. Virol. 71: 127 (1982).PubMedCrossRefGoogle Scholar
  75. 75.
    L. W. Catalano and S. Baron, Protection against herpes-virus and encephalomyocarditis virus encephalitis with a double-stranded RNA inducer of interferon, Proc. Soc. Exp. Biol. Med. 133: 684 (1970).PubMedGoogle Scholar
  76. 76.
    W. A. Blyth, T. A. Hill, H. J. Field, and D. A. Harbour, Reactivation of herpes simplex virus infection by ultraviolet light and possible involvement of prostaglandins, J. Gen. Virol. 33: 547 (1976).PubMedCrossRefGoogle Scholar
  77. 77.
    A. M. Colberg-Poley, H. C. Isom, and F. Rapp, Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus, Proc. Natl. Acad. Sci. USA 76: 5948 (1979).PubMedCrossRefGoogle Scholar
  78. 78.
    B. L. Wigdahl, H. C. Isom, and F. Rapp, Repression and activation of the genome of herpes simplex viruses in human cells, Proc. Natl. Acad. Sci. USA 78: 6522 (1981).PubMedCrossRefGoogle Scholar
  79. 79.
    B. L. Wigdahl, H. C., Isom, E. De Clercq, and F. Rapp, Activation of herpes simplex virus (HSV) type 1 genome by temperature-sensitive mutants of HSV-type 2, Virology 116: 468 (1982).PubMedCrossRefGoogle Scholar
  80. 80.
    E. De Clercq, J. Descamps, P. De Somer, P. J. Barr, A. S. Jones, and R. T. Walker, (E)-5-(2-bromovinyl)-2’-deoxyuridine: a potent and selective anti-herpes agent, Proc. Natl. Acad. Sci. USA 76: 2947 (1979).PubMedCrossRefGoogle Scholar
  81. 81.
    E. De Clercq, J. Descamps, G. Verhelst, R. T. Walker, A. S. Jones, P. F. Torrence, and D. Shugar, Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus, J. Infect. Dis. 141: 563 (1980).PubMedCrossRefGoogle Scholar
  82. 82.
    B. L. Wigdahl, A. C. Scheck, E. De Clercq, and F. Rapp, High efficiency latency and reactivation of herpes simplex virus in human cells, Science 217: 1145 (1982).PubMedCrossRefGoogle Scholar
  83. 83.
    B. L. Wigdahl, R. J. Ziegler, M. Sneve, and F. Rapp, Herpes simplex virus latency and reactivation in isolated rat sensory neurons, Virology 127: 159 (1983).PubMedCrossRefGoogle Scholar
  84. 84.
    L. D. Gelb, J. J. Huang, and W. J. Wellinghoff, Varicella-zoster virus transformation of hamster embryo cells, J. Gen. Virol. 51: 171 (1980).PubMedCrossRefGoogle Scholar
  85. 85.
    K. Yamanishi, Y. Matsunaga, Y., T. Ogino, P. Lopetegui, Biochemical transformation of mouse cells by varicella-zoster virus, J. Gen. Virol. 56: 421 (1981).PubMedCrossRefGoogle Scholar
  86. 86.
    G. Miller, Oncogenesis by Epstein-Barr virus, in: “The Human Herpesvirus: An Interdisciplinary Perspective,” A. J. Nahmias, W. R. Dowdle and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  87. 87.
    H. zur Hausen, H. Schulte-Holthausen, G. Klein, W. Henle, G. Henle, P. Clifford, and L. Santesson, EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the naso-pharynx, Nature (London) 228: 1056 (1970).CrossRefGoogle Scholar
  88. 88.
    M. A. Epstein, R. D. Hunt, and H. Rabin, Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus). I. Retículoproliferative disease in an inoculated animal, Int. J. Cancer 12: 309 (1973).PubMedCrossRefGoogle Scholar
  89. 89.
    T. Dambaugh, C. Beisel, M. Hummel, W. King, S. Fennewald, A. Cheung, M. Heller, N. Raab-Traub, and E. Kieff, Epstein-Barr virus (B95–8) DNA. VII. Molecular cloning and detailed mapping, Proc. Natl. Acad. Sci. USA 77: 2999 (1980).PubMedCrossRefGoogle Scholar
  90. 90.
    G. R. Pearson and L. Aurelian, Immunology of herpesvirusassociated cancers, in: “The Human Herpesviruses: An Interdisciplinary Perspective,” A. J. Nahmías, W. R. Dowdle and R. F. Schinazi, eds., Elsevier, New York (1981).Google Scholar
  91. 91.
    N. J. Maitland, J. H. Kinross, A. Busuttel, S. M. Ludgate, G. E. Smart, and K. W. Jones, The detection of DNA tumour virus-specific RNA sequences in abnormal human cervical biopsies by in situ hybridization, J. Gen. Viral. 55: 123 (1981).CrossRefGoogle Scholar
  92. 92.
    F. Rapp, J. H. Li, and M. Jerkofsky, Transformation of mammalian cells by DNA-containing viruses following photo-dynamic inactivation, Virology 55: 339 (1973).PubMedCrossRefGoogle Scholar
  93. 93.
    R. Duff and F. Rapp, Properties of hamster embryo fibroblasts transformed in vitro after exposure to ultraviolet-irradiated herpes simplex virus type 2, J. Virol. 8: 469 (1971).PubMedGoogle Scholar
  94. 94.
    R. Duff and F. Rapp, Oncogenic transformation of hamster embryo cells after exposure to inactivated herpes simplex virus type I, J. Virol. 12: 209 (1973).PubMedGoogle Scholar
  95. 95.
    A. Camacho and P. G. Spear, Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome, Cell 15: 993 (1978).PubMedCrossRefGoogle Scholar
  96. 96.
    G. R. Reyes, R. LaFemina, S. D. Hayward, and G. S. Hayward, Morphological transformation by DNA fragments of human herpesviruses: evidence for two distinct transforming regions in HSV types 1 and 2 and lack of correlation with biochemical transfer of the thymidine kinase gene, Cold Spring Harbor Symp. Quant. Biol. 44: 629 (1980).CrossRefGoogle Scholar
  97. 97.
    R. J. Jariwalla, L. Aurelian, P. 0. P. Ts’0, Tumorígenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2, Proc. Natl. Acad. Sci. USA 77: 2279 (1980).PubMedCrossRefGoogle Scholar
  98. 98.
    D. A. Galloway and J. K. McDougall, Transformation of rodent cells by a cloned DNA fragment of herpes simplex virus type 2, J. Vírol. 38: 749 (1981).PubMedGoogle Scholar
  99. 99.
    G. Giraldo, E. Beth, and E.-S. Huang, Kaposi’s sarcoma and its relationship to cytomegalovirus (CMV). III. CMV DNA and CMV early antigens in Kaposi’s sarcoma, Int. J. Cancer 26: 23 (1980).PubMedCrossRefGoogle Scholar
  100. 100.
    L. Geder, R. Lausch, F. O’Neill, and F. Rapp, Oncogenic transformation of human embryo lung cells by human cytomegalovirus, Science 192: 1134 (1976).PubMedCrossRefGoogle Scholar
  101. 101.
    T. Albrecht and F. Rapp, Malignant transformation of hamster embryo fibroblasts following exposure to ultravirolet-irradiated human cytomegalovírus, Virology 55: 53 (1973).PubMedCrossRefGoogle Scholar
  102. 102.
    A. E. Churchill, L. N. Payne and R. C. Chubb, Immunization against Marek’s disease using a live attenuated virus, Nature (London) 221: 744 (1969).CrossRefGoogle Scholar
  103. 103.
    B. Rager-Zisman and A. C. Allison, Mechanism of immunologic resistance to herpes simplex virus 1 (HSV-1) infection, J. Immunol. 116: 35 (1976).PubMedGoogle Scholar
  104. 104.
    S. Baron, M. G. Worthington, J. Williams and J. W. Gaines, Postexposure serum prophylaxis of neonatal herpes simplex virus infection of mice, Nature (London) 261: 505 (1976).CrossRefGoogle Scholar
  105. 105.
    J. Costa, A. S. Rabson, C. Yee, and T. S. Tralka, Immunoglobulin binding to herpesvirus-induced Fc receptors inhibits virus growth, Nature (London) 269: 251 (1977).CrossRefGoogle Scholar
  106. 106.
    A. Vaheri and K. Cantell, The effect of heparin on herpes simplex virus, Virology 21: 661 (1963).PubMedCrossRefGoogle Scholar
  107. 107.
    A. J. Nahmías and S. Kibrick, Inhibitory effect of heparin on herpes simplex virus, J. Bacteriol. 87: 1060 (1964).PubMedGoogle Scholar
  108. 108.
    J. J. McSharry, L. A. Caliguiri, and H. J. Eggers, Inhibition of uncoating of poliovirus by arildone, a new antiviral drug, Virology 97: 307 (1979).PubMedCrossRefGoogle Scholar
  109. 109.
    L. A. Calíguiri, J. J. McSharry, and G. W. Lawrence, Effect of arildone on modifications of poliovirus in vitro, Virology 105: 86 (1980).PubMedCrossRefGoogle Scholar
  110. 110.
    F. Pancic, B. A. Steinberg, G. D. Diana, P. M. Carabateas, W. G. Gorman, and P. E. Came, Antiviral activity of win 41258–3, a pyrazole compound, against herpes simplex virus in mouse genital infection and in guinea pig skin infection, Antimicrob. Agents Chemother. 19: 470 (1981).CrossRefGoogle Scholar
  111. 111.
    S. Kit, D. R. Dubbs, and M. Anken, Altered physical properties of thymidine kinase after infection of mouse fibroblast cells with herpes simplex virus, J. Virol. 1: 238 (1967).PubMedGoogle Scholar
  112. 112.
    A. T. Jamison, G. A. Gentry, and J. Subak-Sharpe, Induction of both thymidine and deoxycytídine kinase activity by herpes viruses, J. Gen. Vírol. 24: 465 (1974).CrossRefGoogle Scholar
  113. 113.
    H. M. Keír, J. Subak-Sharpe, W. I. H. Shedden, D. H. Watson, and P. Wildy, Immunological evidence for a specific DNA polymerase produced after infection by herpes simplex virus, Virology 30: 154 (1966).PubMedCrossRefGoogle Scholar
  114. 114.
    Y. -C. Cheng, G. Dutschman, E. De Clercq, A. S. Jones, S. G. Rahim, G. Verhelst, and R. T. Walker, Differential affinities of 5-(2-halogenovinyl)-2’-deoxyuridines for deoxythymidine kinases of various origins, Mol. Pharmacol. 20: 230 (1981).PubMedGoogle Scholar
  115. 115.
    K. A. Watanabe, U. Reichman, K. Hírota, C. Lopez, and J. J. Fox, Nucleosides. 110. Synthesis and antíherpes virus activity of some 2’-fluoro-2’-deoxyarabinofuranosylpyrimidine nucleosides, J. Med. Chem. 22: 21 (1979).PubMedCrossRefGoogle Scholar
  116. 116.
    G. B. Elion, P. A. Furman, J. A. Fyfe, P. De Miranda., L. Beauchamp, and H. J. Schaeffer, Selectivity of action of an antíherpetic agent, 9-(2-hydroxyethoxymethyl) guanine, Proc. Natl. Acad. Sci. USA 74: 5716 (1977).PubMedCrossRefGoogle Scholar
  117. 117.
    M. S. Chen and W. H. Prusoff, Association of thymidylate kinase activity with pyrimidine deoxyribonucleoside kinase induced by herpes simplex virus, J. Biol. Chem. 253: 1325 (1978).PubMedGoogle Scholar
  118. 118.
    J. Descamps and E. De Clercq, Specific phosphorylation of E-5-(2-iodovinyl)-2’-deoxyuridine by herpes simplex virus-infected cells, J. Biol. Chem. 256: 5973 (1981).PubMedGoogle Scholar
  119. 119.
    J. A. Fyfe, Differential phosphorylation of (E)-5-(2-bromovinyl)-2’-deoxyuridine monophosphate by thymidylate kinases from herpes simplex viruses type 1 and 2 and varicella-zoster virus, Mol. Pharmacol. 21: 432 (1982).PubMedGoogle Scholar
  120. 120.
    F. Wohlrab, D. R. Mayo, G. D. Hsiung, and B. Francke, Correlation of the expression of deoxypyrimidine triphosphatase with sensitivity to E-5-bromovinyl-2’-deoxyuridine in clinical isolates of herpes simplex virus type 1 and type 2, in: “International Workshop on Herpesviruses,” A. S. Kaplan, M. La Placa, F. Rapp and B. Roizman, eds., Esculapío Publishing Co., Bologna (1981).Google Scholar
  121. 121.
    J. A. Fyfe, P. M. Keller, P. A. Furman, R. L. Miller, and G. B. Elion, Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl) guanine, J. Biol. Chem. 253: 8721 (1978).PubMedGoogle Scholar
  122. 122.
    E.-C. Mar, P. C. Patel, and E.-S. Huang, Effect of 9-(2-hydroxyethoxymethyl) guanine on viral-specific polypeptide synthesis in human cytomegalovirus-infected cells, Am. J. Med. 73: 82 (1982).PubMedCrossRefGoogle Scholar
  123. 123.
    G. B. Elion, Mechanism of action and selectivity of acyclovir, Am. J. Med. 73: 7 (1982).PubMedCrossRefGoogle Scholar
  124. 124.
    H. S. Allaudeen, J. W. Kozarich, J. R. Bertino, and E. De Clercq, On the mechanism of selective inhibition of herpes-virus replication by (E)-5-(2-bromovinyl)-2’-deoxyuridine, Proc. Natl. Acad. Sci USA 78: 2698 (1981).PubMedCrossRefGoogle Scholar
  125. 125.
    E. De Clercq, BVDU, (E)-5-(2-bromovinyl)-2’-deoxyuridine, in: “Antiviral Drugs and Interferon: The Molecular Basis of Their Activity,” Y. Becker, ed., Martinus Níjhoff, The Hague (1982).Google Scholar
  126. 126.
    P. A. Furman, P. V. McGuirt, P. M. Keller, J. A. Fyfe, and G. B. Elion, Inhibition by acyclovír of cell growth and DNA synthesis of cells biochemically transformed with herpesvirus genetic information, Virology 102: 420 (1980).PubMedCrossRefGoogle Scholar
  127. 127.
    H. S. Allaudeen, M. S. Chen, J. J. Lee, E. De Clercq, and W. H. Prusoff, Incorporation of E-5-(2-halovinyl)-2’deoxyuridines into deoxyribonucleic acids of herpes simplex virus type 1-infected cells, J. Biol. Chem. 257: 603 (1982).PubMedGoogle Scholar
  128. 128.
    J. L. Ruth and Y.-C. Cheng, Nucleoside analogues with clinical potential in antivirus chemotherapy. The effect of several thymidine and 2’-deoxycytídine analogue 5’-triphosphates on purified human (a,ß) and herpes simplex virus (types 1, 2) DNA polymerases, Mol. Pharmacol. 20: 415 (1981).PubMedGoogle Scholar
  129. 129.
    W. R. Mancini, E. De Clercq, and W. H. Prusoff, The relationship between incorporation of E-5-(2-bromovinyl)-2’-deoxy-uridine into herpes simplex virus type 1 DNA with virus infectivity and DNA integrity, J. Biol. Chem. 258: 792 (1983).PubMedGoogle Scholar
  130. 130.
    J. Descamps, R. K. Sehgal, E. De Clercq, and H. S. Allaudeen, Inhibitory effect of E-5-(2-bromovinyl)-1–0-D-arabinofuranosyluracil on herpes simplex virus replication and DNA synthesis, J. Virol 43: 332 (1982).PubMedGoogle Scholar
  131. 131.
    E. De Clercq, Selective antiherpes agents, Trends Pharmacol. Sci. 3: 492 (1982).CrossRefGoogle Scholar
  132. 132.
    S. S. Leinbach, J. M. Reno, L. F. Lee, A. F. Isbell, and J. A. Boezi, Mechanism of phosphonoacetate inhibition of herpesvirus-induced DNA polymerase, Biochemistry 15: 426 (1976).PubMedCrossRefGoogle Scholar
  133. 133.
    J. A. Boezi, The antiherpesvirus action of phosphonoacetíc acid, Pharmacol. Ther. 4: 231 (1979).Google Scholar
  134. 134.
    D. M. Coen, P. A. Schaffer, P. A. Furman, P. M. Keller, and M. H. St. Clair, Biochemical and genetic analysis of acyclovir-resistant mutants of herpes simplex virus type 1, Am. J. Med. 73: 351 (1982).PubMedCrossRefGoogle Scholar
  135. 135.
    D. G. Streeter, J. T. Witkowski, G. P. Khare, R. W. Sidwell, R. J. Bauer, R. K. Robbins, and L. N. Simon, Mechanism of action of 1–13-D-ribofuranosyl-1,2,4,triazole-3-carboxamide (vivazole). A new broad spectrum antiviral agent, Proc. Natl. Acad. Sci. USA 70: 1174 (1973).PubMedCrossRefGoogle Scholar
  136. 136.
    B. Oberg and E. Helgstrand, Selective inhibition of viral polymerases by ribavirin triphosphate, in: “Current Chemotherapy,” Vol. 1, W. Síegenthales and R. Lathy, eds., American Society for Microbiology, Washington, D. C. (1978).Google Scholar
  137. 137.
    C. E. Samuel, Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase possessing site specificity similar to heminregulated rabbit retículocyte kinase, Proc. Natl. Acad. Sci. USA 76: 600 (1979).PubMedCrossRefGoogle Scholar
  138. 138.
    I. M. Kerr and R. E. Brown, pppA2’p5’A2’p5’A: An inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells, Proc. Natl. Acad. Sci. USA 75: 256 (1978).PubMedCrossRefGoogle Scholar
  139. 139.
    A. Schmidt, Y. Chernajovsky, L. Shulman, P. Federman, H. Berissi, and M. Revel, An interferon-induced phosphodiesterase degrading (2’,5’) oligoisoadenylate and C-C-A terminus of t-RNA, Proc. Natl. Acad. Sci. USA 76: 4788 (1979).PubMedCrossRefGoogle Scholar
  140. 140.
    P. Gordon and E. R. Brown, The antiviral activity of isoprinosine, Can. J. Microbiol. 18: 1463 (1972).PubMedCrossRefGoogle Scholar
  141. 141.
    P. Gordon, B. Ronsen, and E. R. Brown, Anti-herpesvirus action of isoprinosine, Antimicrob. Agents Chemother. 5: 153 (1974).CrossRefGoogle Scholar
  142. 142.
    K. D. Radsak and D. Weber, Effect of 2-deoxy-D-glucose on cytomegalovirus-induced DNA synthesis in human fibroblasts, J. Gen. Virol. 57: 33 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Fred Rapp
    • 1
  • Brian Wigdahl
    • 1
  1. 1.Department of Microbiology and Cancer Research CenterThe Pennsylvania State University College of MedicineHersheyUSA

Personalised recommendations