1887

Abstract

Herpes simplex virus type 1 (HSV-1) infection induces the selective shut-off of host protein synthesis, other than ribosomal proteins, and the successive synthesis of viral proteins. Because viral mRNAs persist in the cytoplasm after viral protein synthesis has been inhibited, we hypothesized that viral gene expression may be under translational control. Expression of genes encoding immediate early ICP27, early DBP and late US11 proteins, together with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was monitored over the course of infection at the level of mRNA and protein synthesis. After an efficient synthesis beginning with the appearance of successive viral mRNAs in the cytoplasm, synthesis of viral proteins was shut off similarly to the synthesis of GAPDH. This shut-off was not achieved by mRNA degradation but by progressive shifts of viral mRNAs from large polyribosomes to smaller ones, then to 40S ribosomal subunits. Transient expression of the UL41 gene alone, directing synthesis of virion-associated host shut-off (VHS) protein, induced efficient mRNA degradation, but did not impair recruitment of the remaining GAPDH and -actin mRNAs into polyribosomes. These results indicate that HSV-1 induces a selective repression of initiation of mRNA translation which is probably the main cause of the shut-off of viral protein synthesis, and which contributes to the repression of host protein synthesis. VHS protein is not directly involved in this repression, at least in the absence of other viral proteins.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-11-2765
1998-11-01
2022-10-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/11/9820153.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-11-2765&mimeType=html&fmt=ahah

References

  1. Amaldi F., Pierandrei-Amaldi P. 1997; Top genes: a translationally controlled class of genes including those coding for ribosomal proteins. Progress in Molecular and Subcellular Biology 18:1–17
    [Google Scholar]
  2. Arsenakis M., Campadelli-Fiume G., Roizman B. 1988; Regulation of glycoprotein D synthesis: does alpha 4, the major regulatory protein of herpes simplex virus 1, regulate late genes both positively and negatively?. Journal of Virology 62:146–158
    [Google Scholar]
  3. Batterson W., Roizman B. 1983; Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. Journal of Virology 46:371–377
    [Google Scholar]
  4. Campbell M. E. M., Palfreyman J. W., Preston C. M. 1984; Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate-early transcription. Journal of Molecular Biology 180:1–19
    [Google Scholar]
  5. Chou J., Chen J. J., Gross M., Roizman B. 1995; Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 1 34.5-mutants of herpes simplex virus 1. Proceedings of the National Academy of Sciences, USA 92:10516–10520
    [Google Scholar]
  6. Diaz J.-J., Simonin D., Massé T., Deviller P., Kindbeiter K., Denoroy L., Madjar J.-J. 1993; The herpes simplex virus type 1 US11 gene product is a phosphorylated protein found to be non-specifically associated with both ribosomal subunits. Journal of General Virology 74:397–406
    [Google Scholar]
  7. Diaz J.-J., Duc Dodon M., Schaerer-Uthurralt N., Simonin D., Kindbeiter K., Gazzolo L., Madjar J.-J. 1996; Post-transcriptional transactivation of human retroviral envelope glycoprotein expression by herpes simplex virus Us11 protein. Nature 379:273–277
    [Google Scholar]
  8. Elshiekh N. A., Harris-Hamilton E., Bachenheimer S. L. 1991; Differential dependence of herpes simplex virus immediate-early gene expression on de novo-infected cell protein synthesis. Journal of Virology 65:6430–6437
    [Google Scholar]
  9. Ercolani L., Florence B., Denaro M., Kong X., Kang I., Alexander M. 1988; Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. Journal of Biological Chemistry 263:15335–15341
    [Google Scholar]
  10. Fenwick M. L. 1977; A radiation-sensitive host function required for initiation of herpes viral protein synthesis. Virology 77:860–862
    [Google Scholar]
  11. Fenwick M. L., Clark J. 1982; Early and delayed shut-off of host protein synthesis in cells infected with herpes simplex virus. Journal of General Virology 61:121–125
    [Google Scholar]
  12. Fenwick M. L., Owen S. A. 1988; On the control of immediate early (α) mRNA survival in cells infected with herpes simplex virus. Journal of General Virology 69:2869–2877
    [Google Scholar]
  13. Fenwick M. L., Walker M. J. 1979; Phosphorylation of a ribosomal protein and of virus-specific proteins in cells infected with herpes simplex virus. Journal of General Virology 45:397–405
    [Google Scholar]
  14. Garcin D., Massé T., Madjar J.-J., Jacquemont B. 1990; Herpes simplex virus type 1 immediate-early gene expression and shut off of host protein synthesis are inhibited in neomycin-treated human epidermoid carcinoma 2 cells. European Journal of Biochemistry 194:279–286
    [Google Scholar]
  15. Godowski P. J., Knipe D. M. 1986; Transcriptional control of herpesvirus gene expression: gene functions required for positive and negative regulation. Proceedings of the National Academy of Sciences, USA 83:256–260
    [Google Scholar]
  16. Goldin A. L., Sandri-Goldin R. M., Levine M., Glorioso J. C. 1981; Cloning of herpes simplex virus type 1 sequences representing the whole genome. Journal of Virology 38:50–58
    [Google Scholar]
  17. Goodrich L. D., Rixon F. J., Parris D. S. 1989; Kinetics of expression of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1. Journal of Virology 63:137–147
    [Google Scholar]
  18. Greco A., Simonin D., Diaz J.-J., Barjhoux L., Kindbeiter K., Madjar J.-J., Massé T. 1994; The DNA sequence coding for the 5′ untranslated region of herpes simplex type 1 ICP22 mRNA mediates a high level of gene expression. Journal of General Virology 75:1693–1702
    [Google Scholar]
  19. Greco A., Laurent A. M., Madjar J.-J. 1997; Repression of β-actin synthesis and persistence of ribosomal protein synthesis after infection of HeLa cells by herpes simplex virus type 1 are under translational control. Molecular and General Genetics 256:320–327
    [Google Scholar]
  20. Guzowski J. F., Wagner E. K. 1993; Mutation analysis of the herpes-simplex virus type-1 strict late UL38 promoter/leader reveals two regions critical in transcriptional regulation. Journal of Virology 67:5098–5108
    [Google Scholar]
  21. Hanahan D. 1983; Studies on transformation of E. coli with plasmids. Journal of Molecular Biology 166:557–580
    [Google Scholar]
  22. Hardwicke M., Sandri-Goldin S. K. 1994; The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection. Journal of Virology 68:4797–4810
    [Google Scholar]
  23. Homa F. L., Krikos A., Glorioso J. C., Levine M. 1991; Functional analysis of regulatory regions controlling strict late HSV gene expression. In Herpesvirus Transcription and Its Regulation pp. 207–222 Wagner E. K. Edited by Boca Raton, FL: CRC Press;
    [Google Scholar]
  24. Honess R. W., Roizman B. 1973; Protein 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. Journal of Virology 12:1347–1365
    [Google Scholar]
  25. Honess R. W., Roizman B. 1974; Regulation of herpes virus macromolecular synthesis. Cascade regulation of the synthesis of the three groups of viral proteins. Journal of Virology 14:8–19
    [Google Scholar]
  26. Jefferies H. B. J., Reinhard C., Kozma S. C., Thomas G. 1994; Rapamycin selectively represses translation of the ‘polypyrimidine tract’ mRNA family. Proceedings of the National Academy of Sciences, USA 91:4441–4445
    [Google Scholar]
  27. Johnson D. C., Spear P. G. 1984; Evidence for translational regulation of herpes simplex virus type 1 gD expression. Journal of Virology 51:389–394
    [Google Scholar]
  28. Johnson P. A., MacLean C., Marsden H. S., Dalziel R. G., Everett R. D. 1986; The product of gene US11 of herpes simplex virus type 1 is expressed as a true late gene. Journal of General Virology 67:871–883
    [Google Scholar]
  29. Johnson P., Best M., Friedmann T., Parris D. 1991; Isolation of a herpes simplex virus type 1 mutant deleted for the essential UL42 gene and characterization of its null phenotype. Journal of Virology 65:700–710
    [Google Scholar]
  30. Jones F. E., Smibert C. A., Smiley J. R. 1995; Mutational analysis of the herpes simplex virus virion host shutoff protein: evidence that the vhs functions in the absence of other viral protein. Journal of Virology 69:4863–4871
    [Google Scholar]
  31. Kawaguchi Y., Bruni R., Roizman B. 1997; Interaction of herpes simplex virus 1 alpha regulatory protein ICP0 with elongation factor 1delta: ICP0 affects translational machinery. Journal of Virology 71:1019–1024
    [Google Scholar]
  32. Kennedy I. M., Stevely W. S., Leader D. P. 1981; Phosphorylation of ribosomal proteins in hamster fibroblasts infected with pseudorabies virus or herpes simplex virus. Journal of Virology 39:359–366
    [Google Scholar]
  33. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
    [Google Scholar]
  34. McGeoch D. J., Dolan A., Donald S., Rixon F. J. 1985; Sequence determination and genetic content of the short unique region in the genome of herpes simplex type 1 virus. Journal of Molecular Biology 181:1–13
    [Google Scholar]
  35. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. 1988; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
    [Google Scholar]
  36. McLauchlan J., Phelan A., Loney C., Sandri-Goldin R. M., Clements J. B. 1992; Herpes simplex virus IE63 acts at the posttranscriptional level to stimulate viral mRNA 3′ processing. Journal of Virology 66:6939–6945
    [Google Scholar]
  37. McMahan L., Schaffer P. A. 1990; The repressing and enhancing functions of the herpes simplex virus regulatory protein ICP27 map to the C-terminal regions and are required to modulate viral gene expression very early in infection. Journal of Virology 64:3471–3485
    [Google Scholar]
  38. Masse T., Garcin D., Jacquemont B., Madjar J.-J. 1990a; Herpes simplex virus type-1-induced stimulation of ribosomal protein S6 phosphorylation is inhibited in neomycin-treated human epidermoid carcinoma 2 cells and in ras-transformed cells. European Journal of Biochemistry 194:287–291
    [Google Scholar]
  39. Masse T., Garcin D., Jacquemont B., Madjar J.-J. 1990b; Ribosome and protein synthesis modifications after infection of human epidermoid carcinoma cells with herpes simplex virus type 1. Molecular and General Genetics 220:1–12
    [Google Scholar]
  40. Mathews M. B. 1996; Interactions between viruses and the cellular machinery for protein synthesis. In Translational Control pp. 505–548 Hershey J. W. B., Mathews M. B., Sonenberg N. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  41. Mathews M. B., Sonenberg N., Hershey J. W. B. 1996; Origins and targets of translational control. In Translational Control pp. 1–29 Hershey J. W. B., Mathews M. B., Sonenberg N. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  42. Meyuhas O., Ávni D., Shama S. 1996; Translational control of ribosomal protein mRNAs in eukaryotes. In Translational Control pp. 363–389 Hershey J. W. B., Mathews M. B., Sonenberg N. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  43. Nishioka Y., Silverstein S. 1977; Degradation of cellular mRNA during infection by herpes simplex virus. Proceedings of the National Academy of Sciences, USA 74:2370–2374
    [Google Scholar]
  44. Oroskar A. A., Read G. S. 1989; Control of mRNA stability by the virion host shutoff function of herpes simplex virus. Journal of Virology 63:1897–1906
    [Google Scholar]
  45. Overton H., McMillan D., Hope L., Wong-Kai-In P. 1994; Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene. Virology 202:97–106
    [Google Scholar]
  46. Read G. S., Frenkel N. 1983; Herpes simplex virus mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (immediate early) viral polypeptides. Journal of Virology 46:498–512
    [Google Scholar]
  47. Rice S. A., Knipe D. M. 1990; Genetic evidence for two distinct transactivation functions of the herpes simplex virus alpha protein ICP27. Journal of Virology 64:1704–1715
    [Google Scholar]
  48. Roizman B., Sears A. E. 1993; Herpes simplex viruses and their replication. In The Human Herpes Viruses, 3rd edn. pp. 11–68 Roizman B., Whitley R. J., Lopez C. Edited by New York: Raven Press;
    [Google Scholar]
  49. Roller R. J., Roizman B. 1992; The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits. Journal of Virology 66:3624–3632
    [Google Scholar]
  50. Sacks W. R., Greene C. C., Ashman D. P., Schaffer P. A. 1985; Herpes simplex virus type 1 ICP27 is an essential regulatory protein. Journal of Virology 55:796–805
    [Google Scholar]
  51. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  52. Sandri-Goldin R. M., Mendoza G. E. 1992; A herpes virus regulatory protein appears to act post-transcriptionally by affecting mRNA processing. Genes and Development 6:848–863
    [Google Scholar]
  53. Sandri-Goldin R. M., Goldin A. L., Holland L. E., Glorioso J. C., Levine M. 1983; Expression of herpes simplex virus beta and gamma genes integrated in mammalian cells and their induction by an alpha gene product. Molecular and Cellular Biology 3:2028–2044
    [Google Scholar]
  54. Schek N., Bachenheimer S. L. 1985; Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells. Journal of Virology 55:601–610
    [Google Scholar]
  55. Schenck P., Pietschmann S., Gelderblom H., Pauli G., Ludwig H. 1988; Monoclonal antibodies against herpes simplex virus type 1-infected nuclei defining and localizing the ICP8 protein, 65K DNA-binding protein and polypeptides of the ICP35 family. Journal of General Virology 69:99–111
    [Google Scholar]
  56. Silverstein S., Engelhardt D. L. 1979; Alterations in the protein apparatus of cells infected with herpes simplex virus. Virology 95:334–342
    [Google Scholar]
  57. Simonin D., Diaz J.-J., Kindbeiter K., Denoroy L., Madjar J.-J. 1995a; Phosphorylation of ribosomal protein L30 after herpes simplex virus type 1 infection. Electrophoresis 16:854–859
    [Google Scholar]
  58. Simonin D., Diaz J.-J., Kindbeiter K., Pernas P., Madjar J.-J. 1995b; Phosphorylation of herpes simplex virus type 1 Us11 protein is independent ofviral genome expression. Electrophoresis 16:1317–1322
    [Google Scholar]
  59. Simonin D., Diaz J.-J., Massé T., Madjar J.-J. 1997; Persistence of ribosomal protein synthesis after infection of HeLa cells by herpes simplex virus type 1. Journal of General Virology 78:435–443
    [Google Scholar]
  60. Sinclair M. C., McLauchlan J., Mardsen H., Brown S. M. 1994; Characterization of a herpes simplex virus type 1 deletion variant (1703) which under-produces Vmw63 during immediate early conditions of infection. Journal of General Virology 75:1083–1089
    [Google Scholar]
  61. Strom T., Frenkel N. 1987; Effects of herpes simplex virus on mRNA stability. Journal of Virology 61:2198–2207
    [Google Scholar]
  62. Sydiskis R. J., Roizman B. 1967; The disaggregation of host polyribosomes in productive and abortive infection with herpes simplex virus. Virology 32:678–686
    [Google Scholar]
  63. Weinheimer S. P., McKnight S. L. 1987; Transcriptional and post-transcriptional controls establish the cascade of herpes simplex virus protein synthesis. Journal of Molecular Biology 195:819–833
    [Google Scholar]
  64. Yager D. R., Marcy A. I., Coen D. M. 1990; Translational regulation of herpes simplex virus DNA polymerase. Journal of Virology 64:2217–2225
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-11-2765
Loading
/content/journal/jgv/10.1099/0022-1317-79-11-2765
Loading

Data & Media loading...

Most cited this month 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