1887

Abstract

Stimulation of the Jun NH-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK) is part of the stress-related signal transduction pathways conveying signals from the cell surface into the nucleus in order to initiate programmes of gene expression. Here, it was shown that infection by varicella-zoster virus (VZV) caused a 34-fold increase in activation of JNK/SAPK in the early phase of infection and a 2-fold increase in activation of p38/MAPK in the later phase. The phosphorylation of downstream targets c-Jun and ATF-2 was also increased; subsequent cascades to induce pro-inflammatory responses were significantly activated whereas cascades to activate apoptotic events were not. In the late phase of infection, both JNK/SAPK and p38/MAPK activities were reduced to basal levels. The use of specific inhibitors demonstrated that inhibition of JNK/SAPK resulted in a 2-fold increase in VZV replication whereas a strong decrease in virus replication was observed after inhibition of p38/MAPK. In contrast, constitutive activation of JNK/SAPK resulted in a decline in VZV replication. Blocking gene expression by treating cells with actinomycin D or cycloheximide prior to infection resulted in activation of neither JNK/SAPK nor p38/MAPK. It was assumed that the presence of tegument proteins was not sufficient to activate stress pathways, but that expression of viral genes was necessary. This suggests that activation of stress pathways by VZV infection represents a finely regulated system that activates cellular transcription factors for transregulation of VZV-encoded genes, but prevents activation of cellular defence mechanisms.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80347-0
2004-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/12/vir853529.html?itemId=/content/journal/jgv/10.1099/vir.0.80347-0&mimeType=html&fmt=ahah

References

  1. Andrews N. C., Faller D. V. 1991; A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res 19:2499 [CrossRef]
    [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. 1987; Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729–739 [CrossRef]
    [Google Scholar]
  3. Benn J., Su F., Doria M., Schneider R. J. 1996; Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases. J Virol 70:4978–4985
    [Google Scholar]
  4. Beyaert R., Cuenda A., Vanden Berghe W., Plaisance S., Lee J. C., Haegeman G., Cohen P., Fiers W. 1996; The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. EMBO J 15:1914–1923
    [Google Scholar]
  5. Bonny C., Oberson A., Negri S., Sauser C., Schorderet D. F. 2001; Cell-permeable peptide inhibitors of JNK: novel blockers of β -cell death. Diabetes 50:77–82 [CrossRef]
    [Google Scholar]
  6. Bruder J. T., Kovesdi I. 1997; Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression. J Virol 71:398–404
    [Google Scholar]
  7. Cano E., Hazzalin C. A., Mahadevan L. C. 1994; Anisomycin-activated protein kinases p45 and p55 but not mitogen-activated protein kinases ERK-1 and -2 are implicated in the induction of c-fos and c-jun. Mol Cell Biol 14:7352–7362
    [Google Scholar]
  8. Castellazzi M., Spyrou G., La Vista N., Dangy J. P., Piu F., Yaniv M., Brun G. 1991; Overexpression of c-jun, junB, or junD affects cell growth differently. Proc Natl Acad Sci U S A 88:8890–8894 [CrossRef]
    [Google Scholar]
  9. Derijard B., Hibi M., Wu I. H., Barrett T., Su B., Deng T., Karin M., Davis R. J. 1994; JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:1025–1037 [CrossRef]
    [Google Scholar]
  10. Derijard B., Raingeaud J., Barrett T., Wu I. H., Han J., Ulevitch R. J., Davis R. J. 1995; Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267:682–685 [CrossRef]
    [Google Scholar]
  11. Desloges N., Rahaus M., Wolff M. H. 2004; Varicella-zoster virus does not significantly induce the cell defence mechanism mediated by the 2-5A/RNase L pathway during its replication cycle. Med Microbiol Immunol doi: 10.0007/s00430-004-0220-7
    [Google Scholar]
  12. Gupta S., Campbell D., Derijard B., Davis R. J. 1995; Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267:389–393 [CrossRef]
    [Google Scholar]
  13. Hazzalin C. A., Le Panse R., Cano E., Mahadevan L. C. 1998; Anisomycin selectively desensitizes signalling components involved in stress kinase activation and fos and jun induction. Mol Cell Biol 18:1844–1854
    [Google Scholar]
  14. Hirasawa K., Kim A., Han H. S., Han J., Jun H. S., Yoon J. W. 2003; Effect of p38 mitogen-activated protein kinase on the replication of encephalomyocarditis virus. J Virol 77:5649–5656 [CrossRef]
    [Google Scholar]
  15. Hood C., Cunningham A. L., Slobedman B., Boadle R. A., Abendroth A. 2003; Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: evidence for a cell-type-specific apoptotic response. J Virol 77:12852–12864 [CrossRef]
    [Google Scholar]
  16. Huttunen P., Hyypia T., Vihinen P., Nissinen L., Heino J. 1998; Echovirus 1 infection induces both stress- and growth-activated mitogen-activated protein kinase pathways and regulates the transcription of cellular immediate-early genes. Virology 250:85–93 [CrossRef]
    [Google Scholar]
  17. Iordanov M. S., Paranjape J. M., Zhou A., Wong J., Williams B. R., Meurs E. F., Silverman R. H., Magun B. E. 2000; Activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase by double-stranded RNA and encephalomyocarditis virus: involvement of RNase L, protein kinase R, and alternative pathways. Mol Cell Biol 20:617–627 [CrossRef]
    [Google Scholar]
  18. Ip Y. T., Davis R. J. 1998; Signal transduction by the c-Jun N-terminal kinase (JNK) – from inflammation to development. Curr Opin Cell Biol 10:205–219 [CrossRef]
    [Google Scholar]
  19. Ito H., Sommer M. H., Zerboni L., He H., Boucaud D., Hay J., Ruyechan W., Arvin A. M. 2003; Promoter sequences of varicella-zoster virus glycoprotein I targeted by cellular transactivating factors Sp1 and USF determine virulence in skin and T cells in SCIDhu mice in vivo. J Virol 77:489–498 [CrossRef]
    [Google Scholar]
  20. Kinchington P. R., Vergnes J. P., Defechereux P., Piette J., Turse S. E. 1994; Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63. J Virol 68:3570–3581
    [Google Scholar]
  21. Kumar A., Manna S. K., Dhawan S., Aggarwal B. B. 1998; HIV-Tat protein activates c-Jun N-terminal kinase and activator protein-1. J Immunol 161:776–781
    [Google Scholar]
  22. Kyriakis J. M., Avruch J. 1996; Sounding the alarm: protein kinase cascades activated by stress and inflammation. J Biol Chem 271:24313–24316 [CrossRef]
    [Google Scholar]
  23. Kyriakis J. M., Banerjee P., Nikolakaki E., Dai T., Rubie E. A., Ahmad M. F., Avruch J., Woodgett J. R. 1994; The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156–160 [CrossRef]
    [Google Scholar]
  24. Kyriakis J. M., Woodgett J. R., Avruch J. 1995; The stress-activated protein kinases. A novel ERK subfamily responsive to cellular stress and inflammatory cytokines. Ann N Y Acad Sci 766:303–319 [CrossRef]
    [Google Scholar]
  25. Lawler S., Cuenda A., Goedert M., Cohen P. 1997; SKK4, a novel activator of stress-activated protein kinase-1 (SAPK1/JNK). FEBS Lett 414:153–158 [CrossRef]
    [Google Scholar]
  26. Li C. J., Ueda Y., Shi B., Borodyansky L., Huang L., Li Y.-Z., Pardee A. B. 1997; Tat protein induces self-perpetuating permissivity for productive HIV-1 infection. Proc Natl Acad Sci U S A 94:8116–8120 [CrossRef]
    [Google Scholar]
  27. Li G., Xiang Y., Sabapathy K., Silverman R. H. 2004; An apoptotic signaling pathway in the interferon antiviral response mediated by RNase L and c-Jun NH2-terminal kinase. J Biol Chem 279:1123–1131 [CrossRef]
    [Google Scholar]
  28. Ludwig S., Ehrhardt C., Neumeier E. R., Kracht M., Rapp U. R., Pleschka S. 2001; Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway. J Biol Chem 276:10990–10998 [CrossRef]
    [Google Scholar]
  29. Manthey C. L., Wang S. W., Kinney S. D., Yao Z. 1998; SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes. J Leukoc Biol 64:409–417
    [Google Scholar]
  30. McLean T. I., Bachenheimer S. L. 1999; Activation of cJUN N-terminal kinase by herpes simplex virus type 1 enhances viral replication. J Virol 73:8415–8426
    [Google Scholar]
  31. Meier J. L., Luo X., Sawadogo M., Straus S. E. 1994; The cellular transcription factor USF cooperates with varicella-zoster virus immediate-early protein 62 to symmetrically activate a bidirectional viral promoter. Mol Cell Biol 14:6896–6906
    [Google Scholar]
  32. Miyazawa K., Mori A., Miyata H., Akahane M., Ajisawa Y., Okudaira H. 1998; Regulation of interleukin-1 β -induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase. J Biol Chem 273:24832–24838 [CrossRef]
    [Google Scholar]
  33. Montminy M. 1997; Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66:807–822 [CrossRef]
    [Google Scholar]
  34. Nakatsue T., Katoh I., Nakamura S., Takahashi Y., Ikawa Y., Yoshinaka Y. 1998; Acute infection of Sindbis virus induces phosphorylation and intracellular translocation of small heat shock protein HSP27 and activation of p38 MAP kinase signaling pathway. Biochem Biophys Res Commun 253:59–64 [CrossRef]
    [Google Scholar]
  35. Northrop J. P., Ullman K. S., Crabtree G. R. 1993; Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. J Biol Chem 268:2917–2923
    [Google Scholar]
  36. Patel A., Hanson J., McLean T. I., Olgiate J., Hilton M., Miller W. E., Bachenheimer S. L. 1998; Herpes simplex type 1 induction of persistent NF- κ B nuclear translocation increases the efficiency of virus replication. Virology 247:212–222 [CrossRef]
    [Google Scholar]
  37. Peng H., He H., Hay J., Ruyechan W. T. 2003; Interaction between the varicella zoster virus IE62 major transactivator and cellular transcription factor Sp1. J Biol Chem 278:38068–38075 [CrossRef]
    [Google Scholar]
  38. Pleschka S., Wolff T., Ehrhardt C., Hobom G., Planz O., Rapp U. R., Ludwig S. 2001; Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade. Nat Cell Biol 3:301–305 [CrossRef]
    [Google Scholar]
  39. Popik W., Pitha P. M. 1998; Early activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase in response to binding of simian immunodeficiency virus to Jurkat T cells expressing CCR5 receptor. Virology 252:210–217 [CrossRef]
    [Google Scholar]
  40. Rahaus M., Wolff M. H. 2000; Transcription factor Sp1 is involved in the regulation of varicella-zoster virus glycoprotein E. Virus Res 69:69–81 [CrossRef]
    [Google Scholar]
  41. Rahaus M., Wolff M. H. 2003; Reciprocal effects of varicella-zoster virus (VZV) and AP1: activation of jun, fos and ATF-2 after VZV infection and their importance for the regulation of viral genes. Virus Res 92:9–21 [CrossRef]
    [Google Scholar]
  42. Rahaus M., Desloges N., Yang M., Ruyechan W. T., Wolff M. H. 2003; Transcription factor USF, expressed during the entire phase of varicella-zoster virus infection, interacts physically with the major viral transactivator IE62 and plays a significant role in virus replication. J Gen Virol 84:2957–2967 [CrossRef]
    [Google Scholar]
  43. Robinson M. J., Cobb M. H. 1997; Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9:180–186 [CrossRef]
    [Google Scholar]
  44. Rodems S. M., Spector D. H. 1998; Extracellular signal-regulated kinase activity is sustained early during human cytomegalovirus infection. J Virol 72:9173–9180
    [Google Scholar]
  45. Ruyechan W. T., Hay J. 2000; DNA replication. In Varicella-zoster Virus . Virology and Clinical Management pp  51–73 Edited by Arvin A. M., Gershon A. A. Cambridge: Cambridge University Press;
    [Google Scholar]
  46. Sadzot-Delvaux C., Baudoux L., Defechereux P., Piette J., Rentier B. 1999; Overview of the replication cycle of varicella-zoster virus. In Contributions in Microbiology , vol. 3 Varicella-zoster virus. Molecular Biology, Pathogenesis, and Clinical Aspects pp.  21–42 Edited by Wolff M. H., Schünemann S., Schmidt A. Basel: Karger;
    [Google Scholar]
  47. Sambucetti L. C., Cherrington J. M., Wilkinson G. W., Mocarski E. S. 1989; NF- κ B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J 8:4251–4258
    [Google Scholar]
  48. Seger R., Krebs E. G. 1995; The MAPK signaling cascade. FASEB J 9:726–735
    [Google Scholar]
  49. Whitmarsh A. J., Davis R. J. 1996; Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74:589–607 [CrossRef]
    [Google Scholar]
  50. Yurochko A. D., Hwang E. S., Rasmussen L., Keay S., Pereira L., Huang E. S. 1997; The human cytomegalovirus UL55 (gB) and UL75 (gH) glycoprotein ligands initiate the rapid activation of Sp1 and NF- κ B during infection. J Virol 71:5051–5059
    [Google Scholar]
  51. Zachos G., Clements B., Conner J. 1999; Herpes simplex virus type 1 infection stimulates p38/c-Jun N-terminal mitogen-activated protein kinase pathways and activates transcription factor AP-1. J Biol Chem 274:5097–5103 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80347-0
Loading
/content/journal/jgv/10.1099/vir.0.80347-0
Loading

Data & Media loading...

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