1887

Journal of General Virology header logo

Volume 78, Issue 12

Herpes simplex virus 1716, an ICP 34.5 null mutant, is unable to replicate in CV-1 cells due to a translational block that can be overcome by coinfection with SV40 Free

Abstract

Herpes simplex virus (HSV) mutants lacking the gene encoding infected cell protein (ICP) 34.5 exhibit an attenuated phenotype in models of pathogenesis and have been used for experimental cancer therapy. Recently it was shown that the HSV ICP 34.5 protein functions to prevent the host cell- induced double-stranded RNA-activated protein kinase (PKR)-dependent translational block that normally occurs during virus infection. We now report that an HSV ICP 34.5 mutant called HSV- 1716 is unable to replicate in the simian kidney cell- derived line CV-1, due to a translational block. Moreover, we find that this block can be overcome by simian virus 40 (SV40). This has been shown directly by infecting CV-1 cells with SV40 and HSV- 1716 simultaneously, and indirectly via HSV-1716 infection of COS-1 cells (CV-1 cells transformed by an origin-defective mutant of SV40 that codes for wild-type T antigen). The translational block is restored when infections are done in the presence of the phosphatase inhibitor okadaic acid. These results support, but do not directly prove, contentions that HSV ICP 34.5 interacts with the PKR pathway to restore translation in non-permissive cells, and that SV40 large T antigen has a similar functional role, but acts downstream of the site of ICP 34.5 interaction (eIF2α) in the pathway. Study of this CV-1/COS-1 system should allow further clarification of the virus-host interactions that underlie the restricted replication of HSV-1 ICP 34.5 gene null mutants.

  • Published Online:
© Society for General Microbiology Ltd 1997
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-12-3333
1997-12-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/12/9400985.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-12-3333&mimeType=html&fmt=ahah

References

  1. Bolovan C. A., Sawtell N. M., Thompson R. L. 1994; ICP 34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. Journal of Virology 68:48–55
     [Google Scholar]
  2. Brown S. M., Harland J., MacLean A. R., Podlech J., Clements J. B. 1994; Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2. Journal of General Virology 75:2367–2377
     [Google Scholar]
  3. Chambers R., Gillespie G. Y., Soroceanu L., Andreansky S., Chatterjee S., Chou J., Roizman B., Whitley R. J. 1995; Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma. Proceedings of the National Academy of Sciences, USA 92:1411–1415
     [Google Scholar]
  4. Chou J., Roizman B. 1992; The γ134.5 gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programmed cell death in neuronal cells. Proceedings of the National Academy of Sciences, USA 89:3266–3270
     [Google Scholar]
  5. Chou J., Kern E. R., Whitley R. J., Roizman B. 1990; Mapping of herpes simplex virus neurovirulence to gamma 1 34.5, a gene nonessential for growth in culture. Science 252:1262–1266
     [Google Scholar]
  6. Cohen P., Holmes C., Tsukitani Y. 1990; Okadaic acid: a new probe for the study of cellular regulation. Trends in Biochemical Sciences 15:98–102
     [Google Scholar]
  7. Gluzman Y. 1981; SV40-transformed simian cells support the replication of early SV40 mutants. Cell 23:175–182
     [Google Scholar]
  8. He B., Gross M., Roizman B. 1997; The γ 1 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1a to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proceedings of the National Academy of Sciences, USA 94:843–848
     [Google Scholar]
  9. Hung S.-L., Srinivasan S., Friedman H. M., Eisenberg R. J., Cohen G. H. 1992; The structural basis of C3b binding by glycoprotein C of herpes simplex virus. Journal of Virology 66:4013–4027
     [Google Scholar]
  10. Javier R. T., Thompson R. L., Stevens J. G. 1987; Genetic and biological analyses of a herpes simplex virus intertypic recombinant reduced specifically forneurovirulence. JournalofVirology 61:1978–1984
     [Google Scholar]
  11. Katze M. G. 1995; Regulat ion of the interferon-induced PKR: can viruses cope?. Trends in Microbiology 3:75–78
     [Google Scholar]
  12. Kesari S., Randazzo B. P., Valyi-Nagy T., Huang Q. S., Brown S. M., MacLean A. R., Lee V. M.-Y., Trojanowski J. Q., Fraser N. W. 1995; Therapy of experimental human brain tumors using a neuro-attenuated herpes simplex virus mutant. Laboratory Investigation 73:636–648
     [Google Scholar]
  13. Kucharczuk J. C., Randazzo B. P., Chang M. Y., Amin K. M., Elshami A. A., Sterman D. H., Rizk N. P., Molnar-Kimber K. L., Brown S. M., MacLean A. R., Litzky L. A., Fraser N. W., Albelda S. M., Kaiser L. R. 1997; Use of a ‘replication-restricted’ herpes virus to treat experimental human malignant mesothelioma. Cancer Research 57:466–471
     [Google Scholar]
  14. Lasner T. M., Kesari S., Brown S. M., Lee V. M.-Y., Fraser N. W., Trojanowski J. Q. 1996; Therapy of a murine model of pediatric brain tumors using a herpes simplex virus type-1 ICP34.5 mutant and demonstration of viral replication within the CNS. Journal of Neuropathology and Experimental Neurology 55:1259–1269
     [Google Scholar]
  15. Lord K. A., Hoffman-Liebermann B., Liebermann D. A. 1990; Sequence of MyD116 cDNA: a novel myeloid differentiation primary response gene induced by IL6. Nucleic Acids Research 18:2823–2828
     [Google Scholar]
  16. McGeoch D. J., Barnett B. C. 1991; Neurovirulence factor. Nature 353:609
     [Google Scholar]
  17. MacLean A. R., Ul-Fareed M., Robertson L., Harland J., Brown S. M. 1991; Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. Journal of General Virology 72:631–639
     [Google Scholar]
  18. Markert J. M., Malick A., Coen D. M., Martuza R. L. 1993; Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir. Neurosurgery 32:597–603
     [Google Scholar]
  19. Mathews M. B., Shenk T. 1991; Adenovirus virus-associated RNA and translation control. Journal of Virology 65:5657–5662
     [Google Scholar]
  20. Mckie E. A., MacLean A. R., Lewis A. D., Cruickshank G., Rampling R., Barnett S. C., Kennedy P. G. E., Brown S. M. 1996; Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumors - evaluation of a potentially effective clinical therapy. British Journal of Cancer 74:745–752
     [Google Scholar]
  21. Perng G.-C., Thompson R. L., Sawtell N. M., Taylor W. E., Slanina S. M., Ghiasi H., Kaiwar R., Nesburn A. B., Wechsler S. L. 1995; An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. Journal of Virology 69:3033–3041
     [Google Scholar]
  22. Perng G. C., Ghiasi H., Slanina S. M., Nesburn A. B., Wechsler S. L. 1996; The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1·5 kilobases of the 8·3 kilobase primary transcript. Journal of Virology 70:976–984
     [Google Scholar]
  23. Rajan P., Swaminathan S., Zhu J., Cole C. N., Barber G., Tevethia M. J., Thimmapaya B. 1995; A novel translational regulation function for the simian virus 40 large-T antigen gene. Journal of Virology 69:785–795
     [Google Scholar]
  24. Randazzo B. P., Kesari S., Gesser R. M., Alsop D., Ford J. C., Brown S. M., MacLean A. R., Fraser N. W. 1995; Treatment of experimental intracranial murine melanoma with a neuro-attenuated herpes simplex virus-1 mutant. Virology 211:94–101
     [Google Scholar]
  25. Randazzo B., Kucharczuk J. C., Litzky L., Kaiser L., Brown S., Maclean A., Albelda S., Fraser N. 1996; Herpes simplex 1716 - an ICP 34.5 mutant - is severely replication restricted in human skin xenografts in vivo. Virology 223:392–396
     [Google Scholar]
  26. Randazzo B. P., Bhat M. G., Kesari S., Fraser N. W., Brown S. M. 1997; Treatment of experimental subcutaneous human melanoma with a replication restricted herpes simplex virus mutant. Journal of Investigative Dermatology 108:993–1001
     [Google Scholar]
  27. Spivack J. G., Fraser N. W. 1987; Detection of herpes simplex virus type 1 transcripts during a latent infection in mice. Journal of Virology 61:3841–3847
     [Google Scholar]
  28. Spivack J. G., Fareed M. U., Valyi-Nagy T., Nash T. C., O’Keefe J. S., Gesser R. M., McKie E. A., MacLean A. R., Fraser N. W., Brown S. M. 1995; Replication, establishment of latent infection, expression of the latency-associated transcripts and explant reactivation of herpes simplex virus type 1 γ34.5 mutants in a mouse eye model. Journal of General Virology 76:321–332
     [Google Scholar]
  29. Swaminathan S., Rajan P., Savinova O., Jagus R., Thimmapaya B. 1996; Simian virus 40 large-T bypasses the translational block imposed by the phosphorylation of eIF-2α. Virology 219:321–323
     [Google Scholar]
  30. Taha M. Y., Brown S. M., Clements G. B., Graham D. I. 1990; The JH2604 deletion variant of herpes simplex virus type 2 (HG52) fails to produce necrotizing encephalitis following intracranial inoculation of mice. Journal of General Virology 71:1597–1601
     [Google Scholar]
  31. Tal-Singer R., Lasner T. M., Podrzuckl W., Skokotas A., Leary J. J., Berger S. L., Fraser N. W. 1997; Gene expression during reactivation of herpes simplex virus type 1 from latency in the peripheral nervous system is different from that during lytic infection of tissue cultures. Journal of Virology 71:5268–5276
     [Google Scholar]
  32. Valyi-Nagy T., Fareed M. U., O’Keefe J. S., Gesser R. M., MacLean A. R., Brown S. M., Spivack J. G., Fraser N. W. 1994; The herpes simplex virus type 1 strain 17+ γ34.5 deletion mutant 1716 is avirulent in SCID mice. Journal of General Virology 75:2059–2063
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-12-3333
Loading
Herpes simplex virus 1716, an ICP 34.5 null mutant, is unable to replicate in CV-1 cells due to a translational block that can be overcome by coinfection with SV40
J. Gen. Virol. 78, 3333 (1997); https://doi.org/10.1099/0022-1317-78-12-3333
/content/journal/jgv/10.1099/0022-1317-78-12-3333
/content/journal/jgv/10.1099/0022-1317-78-12-3333
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error