Advertisement

Antiviral Effects of Herpes Simplex Virus Specific Anti-Sense Nucleic Acids

  • Edouard M. Cantin
  • Gregory Podsakoff
  • Dru E. Willey
  • Harry Openshaw
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 312)

Summary

We have targeted mRNA sequences encompassing the translation initiation codon of the essential herpes simplex virus type 1 (HSV-1) IE3 gene with three kinds of anti-sense molecule. Addition of a 15mer oligodeoxyribonucleoside methylphosphonate to tissue culture cells resulted in suppression of viral replication. HSV-1 replication was also inhibited in cultured cells containing anti-sense vectors expressing transcripts complementary to the IE3 mRNA. We have also constructed a ribozyme which upon base pairing with the target 1E3 mRNA induces cleavage at the predicted GUC site. A major obstacle to anti-sense studies in animals is drug delivery of preformed anti-sense molecules to ganglionic neurons, the site of HSV latency and reactivation. We speculate as to how this may be accomplished through carrier compounds which are taken up by nerve terminals and transported by retrograde axoplasmic flow. By the same route, HSV itself may be used as an anti-sense vector.

Keywords

Trigeminal Ganglion Latency Associate Transcript Immediate Early Recurrent Genital Herpes Herpes Simplex Virus Latency 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Buzayan, J.M., Gerlach, W.L., and Bruening, G., 1986, Satellite tobacco ringspot virus RNA: a subset of the RNA sequence is sufficient for autolytic processing, Proc. Natl. Acad. Sci. USA 83:8859.PubMedCrossRefGoogle Scholar
  2. Chatis, P.A., Miller, C.H., Schrager, L.E., and Crumpacker, C.S., 1989, Successful treatment with foscarnet of an acyclovir-resistant mucocutaneous infection of herpes simplex virus in a patient with acquired immunodeficiency syndrome, N. Engl. J. Med. 320:297.PubMedCrossRefGoogle Scholar
  3. Cantin, E.M., Puga, A., and Notkins, A.L., 1987, Molecular biology of herpes simplex virus latency, in: “Concepts in Viral Pathogenesis,” A.L. Notkins and M.B.A. Oldstone, eds., Springer-Verlag, New York.Google Scholar
  4. Cech, T.R., and Bass, B.A., 1986, Biological catalysis by RNA, Ann Rev. Biochem. 55:599.PubMedCrossRefGoogle Scholar
  5. Coen, D.M., Kosz-Vnenchak, M., Jacobson, J.G., Leib, D.A., Bogard, C.L., Schaffer, P.A., Tyler, K.L., and Knipe, D.M., 1989, Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate, Proc. Natl. Acad. Sci. USA 86:4736.PubMedCrossRefGoogle Scholar
  6. Coleman, J.A., Green, P.J., and Inouye, M., 1984, the use of RNAs complementary to specific mRNAs to regulate the expression of individual bacterial genes, Cell 37:429.PubMedCrossRefGoogle Scholar
  7. Coleman, J.A., Hirashima, A., Inokuchi, Y., Green, P.J., and Inouye, M., 1985, A novel immune system against bacteriophage infection using complementary RNA (mic RNA), Nature 315:601.PubMedCrossRefGoogle Scholar
  8. Corey, L., and Spear, P.G., 1986, Infections with herpes simplex viruses, N. Engl. J. Med. 314:686.PubMedCrossRefGoogle Scholar
  9. Cremer, K.J., Mackett, M. Wohlenberg, C., Notkins, A.L., and Moss, B., 1985, Vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D prevents latent herpes in mice, Science 228:737.PubMedCrossRefGoogle Scholar
  10. Crumpacker, C.S., 1989, Molecular targets of antiviral therapy, N. Engl. J. Med. 321:163.PubMedCrossRefGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. Dobson, A.T., Sedarati, F., Devi-Rao, G., Flanagan, W.M., Farrell, M.J., Stevens, J.G., Wagner, E.K., and Feldman, L.T., 1989, Identification of the latency associated transcript promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus, J. Virol. 63:3844.PubMedGoogle Scholar
  13. Ellis, M.N., Keller, P.M., Fyfe, J.A., Martin, J.L., Rooney, J.F., Straus, S.E., NusinoffLehrman, S., and Barry, D.W., 1987, Clinical isolate of herpes simplex virus type 2 that induces a thymidine kinase with altered substrate specificity, Antimicrob. Agents Chemother. 31:1117.PubMedCrossRefGoogle Scholar
  14. Erlich, K.S., Mills, J., Chatis, P., Mertz, G.J., Busch, D.F., Follansbee, S.E., Grant, R.M., and Crumpacker, C.S., 1989, Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome, N. Engl. J. Med. 320:293.PubMedCrossRefGoogle Scholar
  15. Forster, A.C., and Symons, R.H., 1987, Self-cleavage of plus and minus RNAs of a viusoid and structural model for the active sites, Cell 49:211.PubMedCrossRefGoogle Scholar
  16. Galloway, D.A., and McDougall, J.K., 1983, The oncogenic potential of herpes simplex viruses: evidence for a ‘hit and run’ mechanism, Nature 302:21.PubMedCrossRefGoogle Scholar
  17. Gontas, N.K., Harper, C., Mizutani, T., Gontas, J., 1979, Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport, J. Histochem. Cytochem. 27:728.CrossRefGoogle Scholar
  18. Harper, C.G., Gontas, J.O., Mizutani, T., and Gontas, N.K., 1980, Retrograde transport and effects of toxic ricin in the autonomic nervous system, Lab. Invest. 42:396.PubMedGoogle Scholar
  19. Haseloff, J., and Gerlach, W.L., 1988, Simple RNA enzymes with new and highly specific endoribonuclease activities, Nature 334:585.PubMedCrossRefGoogle Scholar
  20. Hino, M., Sekizawa, T., and Openshaw, H., 1988, Ricin injection eliminates herpes simplex virus in the mouse, J. Infect. Dis. 157:1270.PubMedCrossRefGoogle Scholar
  21. Hirsch, M.C., and Schooley, R.T., 1989, Resistance to antiviral drugs: the end of innocence (editorial), N. Engl. J. Med. 320:313.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. Hutchins, C.J., Rathjen, P.D., Forster, A.C., and Symons, R.H., 1985, Self cleavage of plus and minus RNA transcripts of avocado sunblotch viroid, Nucl. Acid Res. 14:3627.CrossRefGoogle Scholar
  24. Iwasaki, Y., Yamamoto, T., Konno, H., lizuka, H., and Kudo, H., 1986, Eradication of herpes simplex virus persistence in rat trigeminal ganglia by retrograde axoplasmic transport, J. Virol. 59:242.PubMedGoogle Scholar
  25. Izant, J.G., and Weintraub, H., 1984, Inhibition of thymidine kinase gene expression by antisense RNA: a molecular approach to genetic analysis, Cell 36:1007.PubMedCrossRefGoogle Scholar
  26. Knipe, D.M., The role of viral and cellular nuclear proteins in herpes simplex virus replication, Adv. Virus Res. 37:85.Google Scholar
  27. Krol, A.R. van der, Lenting, P.E., Veenstra, J., van der Meer, I.M., Koes, R.E., Gerats, A.G.M., Mol, J.N.M., and Stuitje, A.R., 1988a, An antisense chalcone synthetase gene in transgenic plants inhibits flower pigmentation, Nature 333:866.CrossRefGoogle Scholar
  28. Krol, A.R. van der, Mol, J.N.M., and Stuitje, A.R., 1988b, Modulation of eukaryotic gene expression by complementary RNA and DNA sequences, BioTechniques 6:958.Google Scholar
  29. Kulka, M., Smith, G.C., Aurelian, L., Fishelevich, R., Meade, K., Miller, P., and Ts’s, P.O.P., 1989, Site specificity of the inhibitory effects of oligonucleoside methylphosphonates complementary to the acceptor splice junction of herpes simplex virus type 1 immediate early mRNA 4, Proc. Natl. Acad. Sci. USA 86:6868.PubMedCrossRefGoogle Scholar
  30. Leib, D.A., Bogard, C.L., Kosz-Vnenchak, M., Hicks, K.A., Coen, D.M., Knipe, D.M., and Schaffer, P.A., 1989a, A deletion mutant of the latency associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency, J. Virol. 63:2893.Google Scholar
  31. Meignier, B., Jourdier, T.M., Norrild, B., Pereira, L., and Roizman, B., 1987, Immunization of experimental animals with reconstituted glycoprotein mixtures of herpes simplex virus 1 and 2: protection against challenge with virulent virus, J. Infect. Dis. 155:921.PubMedCrossRefGoogle Scholar
  32. Nusinoff-Lehrman, S., Douglas, J.W., Corey, L., and Barry, D.W., 1986, Recurrent genital herpes and suppressive oral acyclovir therapy: relationship between clinical outcome and in-vitro drug sensitivity, Ann. Intern. Med. 104:786.Google Scholar
  33. 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 proteins of herpes simplex virus in the transactivation of delayed early promoters, J. Virol. 53:751.PubMedGoogle Scholar
  34. Parker, A.C., Craig, J.O., Collins, P., Oliver, N., and Smith, J., 1987, Acyclovirresistant herpes simplex virus infection due to altered DNA polymerase, Lancet 2:1461.PubMedCrossRefGoogle Scholar
  35. Paterson, B.M., Roberts, B.E., and Kuff, E.L., 1977, Structural gene indentification and mapping by DNA-mRNA mediated hybrid-arrest cell-free translation, Proc. Natl. Acad. Sci. USA 74:4370.Google Scholar
  36. Puga, A., and Notkins, A.L., 1987, Continued expression of a poly (A+) transcript of herpes simplex virus type 1 in trigeminal ganglia of latently infected mice, J. Virol. 61:1700.PubMedGoogle Scholar
  37. Roizman, B., 1983, “The Herpesviruses 3”, Plenum Publishing Corporation, New York.CrossRefGoogle Scholar
  38. Roizman, B., and Sears, A.E., 1987, An inquiry into the mechanisms of herpes simplex virus latency, Ann. Rev. Microbiol. 41:543–577.CrossRefGoogle Scholar
  39. Smith, C.C., Aurelian, L., Reddy, P.M., Miller, P.S., and Ts’o, P.O.P., 1986, Antiviral effect of an oligo (nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5, Proc. Natl. Acad. Sci. USA 83:2787.PubMedCrossRefGoogle Scholar
  40. Stanberry, L.R., Bernstein, D.I., Burke, R.L., Pachl, C., and Myers, M.G., 1987, Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes, J. Infect. Dis. 155:914.PubMedCrossRefGoogle Scholar
  41. Steiner, I., Spivak, J.G., Lirette, L.P., et al., 1989, Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection, EMBO Journal 8:505.PubMedGoogle Scholar
  42. Stevens, J.G., 1989, Human herpesvirus: a consideration of the latent state, Microb. Rev. 53:318.Google Scholar
  43. Stevens, J.G., Wagner, E.K., Devi-Rao, G.B., et al., 1987, RNA complementary to a herpes virus alpha gene mRNA is prominent in latently infected neurons, Science 235:1056.PubMedCrossRefGoogle Scholar
  44. Straus, S.E., Takiff, H.E., Seidlin, M., Bachrach, S., Lininger, Di Giovana, J.J., Wester, K.A., Smith, H.A., Lehrman, S.N., Creagh-Kirk, T., and Ailing, D.W., 1984, Suppression of frequently recurring genital herpes: a placebo-controlled double-blind trial of oral acyclovir, N. Engl. J. Med. 310:1545.Google Scholar
  45. Spruance, S.L., Stewart, J.C., Rowe, N.H., McKeough, M.B., Wenerstrom, G., and Freeman, D.J., 1990, Treatment of recurrent herpes simplex labialis with oral acyclovir, J. Infect. Dis. 161:185.PubMedCrossRefGoogle Scholar
  46. Thoenen, H., Barde, Y.A., 1980, Physiology of nerve growth factor, Physiol. Rev. 60:1284.PubMedGoogle Scholar
  47. Ts’o, P.O.P., Miller, P.S., Aurelian, L., Murakami, A., Agris, C., Blake, K.R., Lin, S.B., Lee, B.L., and Smith, C.C., 1987, An approach to chemotherapy based on sequence information and nucleic acid chemistry, in: “Biological Approaches to the Controlled Delivery of Drugs,” Annals N.Y. Acad. Sci. 507:220.Google Scholar
  48. Uhlenbeck, O.C., 1987, A small catalytic oligoribonucleotide, Nature 328:596.PubMedCrossRefGoogle Scholar
  49. Uhlman, E., and Peyman, A., 1990, Antisense oligonucleotides: a new therapeutic principle, Chemical Reviews 90:544.CrossRefGoogle Scholar
  50. Willey, D.E., Cantin, E.M., Hill, L.R., Moss, B., Notkins, A.L., and Openshaw, H., 1988, Herpes simplex virus type 1-vaccinia virus recombinant expressing glycoprotein B: protection from acute and latent infection, J. Infect. Dis. 158:1382.PubMedCrossRefGoogle Scholar
  51. Willey, D.E., Williams, I., Openshaw, H., 1991, Ocular acyclovir delivery by collagen discs: a mouse model to screen anti-viral drugs, Current Eye. Res., In Press.Google Scholar
  52. Wiley, R.G., Blessing, W.W., and Reis, D.J., 1982, Suicide transport: destruction of neurons by retrograde transport of ricin, abrin, and modeccin, Science 216:889.PubMedCrossRefGoogle Scholar
  53. Yamamoto, T., Iwasaki, Y., and Konno, H., 1983, Retrograde axoplasmic transport of toxic lectins is useful for transganglionic tracings of the peripheral nerve, Brain Res. 274:325.PubMedCrossRefGoogle Scholar
  54. Zamencnik, P.C., and Stephenson, M.L., 1978, Inhibition of Rous Sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide, Proc. Natl. Acad. Sci. USA 75:280.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Edouard M. Cantin
    • 1
  • Gregory Podsakoff
    • 1
  • Dru E. Willey
    • 1
  • Harry Openshaw
    • 1
  1. 1.Department of NeurologyCity of Hope National Medical CenterDuarteUSA

Personalised recommendations