1887

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro), a deubiquitinating enzyme, reportedly blocks poly I : C-induced activation of interferon regulatory factor 3 and nuclear factor kappa B, reducing interferon (IFN) induction. This study investigated type I IFN antagonist mechanism of PLpro in human promonocytes. PLpro antagonized IFN-α-induced responses such as interferon-stimulated response element- and AP-1-driven promoter activation, protein kinase R, 2′-5′-oligoadenylate synthetase (OAS), interleukin (IL)-6 and IL-8 expression, and signal transducers and activators of transcription (STAT) 1 (Tyr701), STAT1 (Ser727) and c-Jun phosphorylation. A proteomics approach demonstrated downregulation of extracellular signal-regulated kinase (ERK) 1 and upregulation of ubiquitin-conjugating enzyme (UBC) E2-25k as inhibitory mechanism of PLpro on IFN-α-induced responses. IFN-α treatment significantly induced mRNA expression of UBC E2-25k, but not ERK1, causing time-dependent decrease of ERK1, but not ERK2, in PLpro-expressing cells. Poly-ubiquitination of ERK1 showed a relationship between ERK1 and ubiquitin proteasome signalling pathways associated with IFN antagonism by PLpro. Combination treatment of IFN-α and the proteasome inhibitor MG-132 showed a time-dependent restoration of ERK1 protein levels and significant increase of ERK1, STAT1 and c-Jun phosphorylation in PLpro-expressing cells. Importantly, PD098059 (an ERK1/2 inhibitor) treatment significantly reduced IFN-α-induced ERK1 and STAT1 phosphorylation, inhibiting IFN-α-induced expression of 2′-5′-OAS in vector control cells and PLpro-expressing cells. Overall results proved downregulation of ERK1 by ubiquitin proteasomes and suppression of interaction between ERK1 and STAT1 as type I IFN antagonist function of SARS-CoV PLpro.

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2011-05-01
2024-03-29
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References

  1. Aceves-Luquero C. I., Agarwal A., Callejas-Valera J. L., Arias-González L., Esparís-Ogando A., del Peso Ovalle L., Bellón-Echeverria I., de la Cruz-Morcillo M. A., Galán Moya E. M. et al. 2009; ERK2, but not ERK1, mediates acquired and “de novo” resistance to imatinib mesylate: implication for CML therapy. PLoS ONE 4:e6124 [View Article][PubMed]
    [Google Scholar]
  2. Banninger G., Reich N. C. 2004; STAT2 nuclear trafficking. J Biol Chem 279:39199–39206 [View Article][PubMed]
    [Google Scholar]
  3. Barretto N., Jukneliene D., Ratia K., Chen Z., Mesecar A. D., Baker S. C. 2005; The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J Virol 79:15189–15198 [View Article][PubMed]
    [Google Scholar]
  4. Biron C. A. 2001; Interferons alpha and beta as immune regulators–a new look. Immunity 14:661–664 [View Article][PubMed]
    [Google Scholar]
  5. Caraglia M., Tagliaferri P., Marra M., Giuberti G., Budillon A., Gennaro E. D., Pepe S., Vitale G., Improta S. et al. 2003; EGF activates an inducible survival response via the RAS→Erk-1/2 pathway to counteract interferon-α-mediated apoptosis in epidermoid cancer cells. Cell Death Differ 10:218–229 [View Article][PubMed]
    [Google Scholar]
  6. Deb D. K., Sassano A., Lekmine F., Majchrzak B., Verma A., Kambhampati S., Uddin S., Rahman A., Fish E. N., Platanias L. C. 2003; Activation of protein kinase Cδ by IFN-γ. J Immunol 171:267–273[PubMed] [CrossRef]
    [Google Scholar]
  7. Devaraj S. G., Wang N., Chen Z., Chen Z., Tseng M., Barretto N., Lin R., Peters C. J., Tseng C. T. et al. 2007; Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem 282:32208–32221 [View Article][PubMed]
    [Google Scholar]
  8. Frieman M., Ratia K., Johnston R. E., Mesecar A. D., Baric R. S. 2009; Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-κB signaling. J Virol 83:6689–6705 [View Article][PubMed]
    [Google Scholar]
  9. Gedey R., Jin X. L., Hinthong O., Shisler J. L. 2006; Poxviral regulation of the host NF-κB response: the vaccinia virus M2L protein inhibits induction of NF-κB activation via an ERK2 pathway in virus-infected human embryonic kidney cells. J Virol 80:8676–8685 [View Article][PubMed]
    [Google Scholar]
  10. Giannakopoulos N. V., Luo J. K., Papov V., Zou W., Lenschow D. J., Jacobs B. S., Borden E. C., Li J., Virgin H. W., Zhang D. E. 2005; Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun 336:496–506 [View Article][PubMed]
    [Google Scholar]
  11. He L., Ding Y., Zhang Q., Che X., He Y., Shen H., Wang H., Li Z., Zhao L. et al. 2006; Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 210:288–297 [View Article][PubMed]
    [Google Scholar]
  12. Hoffmann E., Dittrich-Breiholz O., Holtmann H., Kracht M. 2002; Multiple control of interleukin-8 gene expression. J Leukoc Biol 72:847–855[PubMed]
    [Google Scholar]
  13. Hsueh P. R., Chen P. J., Hsiao C. H., Yeh S. H., Cheng W. C., Wang J. L., Chiang B. L., Chang S. C., Chang F. Y. et al. 2004; Patient data, early SARS epidemic, Taiwan. Emerg Infect Dis 10:489–493[PubMed] [CrossRef]
    [Google Scholar]
  14. Huang K. J., Su I. J., Theron M., Wu Y. C., Lai S. K., Liu C. C., Lei H. Y. 2005; An interferon-gamma-related cytokine storm in SARS patients. J Med Virol 75:185–194 [View Article][PubMed]
    [Google Scholar]
  15. Lai C. C., Jou M. J., Huang S. Y., Li S. W., Wan L., Tsai F. J., Lin C. W. 2007; Proteomic analysis of up-regulated proteins in human promonocyte cells expressing severe acute respiratory syndrome coronavirus 3C-like protease. Proteomics 7:1446–1460 [View Article][PubMed]
    [Google Scholar]
  16. Laine A., Ronai Z. 2005; Ubiquitin chains in the ladder of MAPK signaling. Sci STKE 2005:re5 [View Article][PubMed]
    [Google Scholar]
  17. Lee N., Hui D., Wu A., Chan P., Cameron P., Joynt G. M., Ahuja A., Yung M. Y., Leung C. B. et al. 2003; A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348:1986–1994 [View Article][PubMed]
    [Google Scholar]
  18. Lin C. W., Wu C. F., Hsiao N. W., Chang C. Y., Li S. W., Wan L., Lin Y. J., Lin W. Y. 2008; Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71. Int J Antimicrob Agents 32:355–359 [View Article][PubMed]
    [Google Scholar]
  19. Lindner H. A., Fotouhi-Ardakani N., Lytvyn V., Lachance P., Sulea T., Ménard R. 2005; The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. J Virol 79:15199–15208 [View Article][PubMed]
    [Google Scholar]
  20. Lombardi A., Cantini G., Piscitelli E., Gelmini S., Francalanci M., Mello T., Ceni E., Varano G., Forti G. et al. 2008; A new mechanism involving ERK contributes to rosiglitazone inhibition of tumor necrosis factor-alpha and interferon-gamma inflammatory effects in human endothelial cells. Arterioscler Thromb Vasc Biol 28:718–724 [View Article][PubMed]
    [Google Scholar]
  21. Lu Z., Hunter T. 2009; Degradation of activated protein kinases by ubiquitination. Annu Rev Biochem 78:435–475 [View Article][PubMed]
    [Google Scholar]
  22. Lu Z., Xu S., Joazeiro C., Cobb M. H., Hunter T. 2002; The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2. Mol Cell 9:945–956 [View Article][PubMed]
    [Google Scholar]
  23. Malakhov M. P., Kim K. I., Malakhova O. A., Jacobs B. S., Borden E. C., Zhang D. E. 2003; High-throughput immunoblotting. Ubiquitiin-like protein ISG15 modifies key regulators of signal transduction. J Biol Chem 278:16608–16613 [View Article][PubMed]
    [Google Scholar]
  24. Marchi M., D’Antoni A., Formentini I., Parra R., Brambilla R., Ratto G. M., Costa M. 2008; The N-terminal domain of ERK1 accounts for the functional differences with ERK2. PLoS ONE 3:e3873 [View Article][PubMed]
    [Google Scholar]
  25. Marra M. A., Jones S. J., Astell C. R., Holt R. A., Brooks-Wilson A., Butterfield Y. S., Khattra J., Asano J. K., Barber S. A. et al. 2003; The genome sequence of the SARS-associated coronavirus. Science 300:1399–1404 [View Article][PubMed]
    [Google Scholar]
  26. Matsumoto S., Hara T., Hori T., Mitsuyama K., Nagaoka M., Tomiyasu N., Suzuki A., Sata M. 2005; Probiotic Lactobacillus-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells. Clin Exp Immunol 140:417–426 [View Article][PubMed]
    [Google Scholar]
  27. Milella M., Kornblau S. M., Andreeff M. 2003; The mitogen-activated protein kinase signaling module as a therapeutic target in hematologic malignancies. Rev Clin Exp Hematol 7:160–190[PubMed]
    [Google Scholar]
  28. Nicholls J. M., Poon L. L., Lee K. C., Ng W. F., Lai S. T., Leung C. Y., Chu C. M., Hui P. K., Mak K. L., Lim W. 2003; Lung pathology of fatal severe acute respiratory syndrome. Lancet 361:1773–1778 [View Article][PubMed]
    [Google Scholar]
  29. Pagès G., Pouysségur J. 2004; Study of MAPK signaling using knockout mice. Methods Mol Biol 250:155–166[PubMed]
    [Google Scholar]
  30. Ratia K., Saikatendu K. S., Santarsiero B. D., Barretto N., Baker S. C., Stevens R. C., Mesecar A. D. 2006; Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proc Natl Acad Sci U S A 103:5717–5722 [View Article][PubMed]
    [Google Scholar]
  31. Rota P. A., Oberste M. S., Monroe S. S., Nix W. A., Campagnoli R., Icenogle J. P., Peñaranda S., Bankamp B., Maher K. et al. 2003; Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394–1399 [View Article][PubMed]
    [Google Scholar]
  32. Samuel C. E. 2001; Antiviral actions of interferons. Clin Microbiol Rev 14:778–809 [View Article][PubMed]
    [Google Scholar]
  33. Spiegel M., Pichlmair A., Martínez-Sobrido L., Cros J., García-Sastre A., Haller O., Weber F. 2005; Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol 79:2079–2086 [View Article][PubMed]
    [Google Scholar]
  34. Sulea T., Lindner H. A., Purisima E. O., Ménard R. 2005; Deubiquitination, a new function of the severe acute respiratory syndrome coronavirus papain-like protease?. J Virol 79:4550–4551 [View Article][PubMed]
    [Google Scholar]
  35. Tagliaferri P., Caraglia M., Budillon A., Marra M., Vitale G., Viscomi C., Masciari S., Tassone P., Abbruzzese A., Venuta S. 2005; New pharmacokinetic and pharmacodynamic tools for interferon-alpha (IFN-alpha) treatment of human cancer. Cancer Immunol Immunother 54:1–10 [View Article][PubMed]
    [Google Scholar]
  36. Tang X., Gao J. S., Guan Y. J., McLane K. E., Yuan Z. L., Ramratnam B., Chin Y. E. 2007; Acetylation-dependent signal transduction for type I interferon receptor. Cell 131:93–105 [View Article][PubMed]
    [Google Scholar]
  37. Thiel V., Ivanov K. A., Putics A., Hertzig T., Schelle B., Bayer S., Weissbrich B., Snijder E. J., Rabenau H. et al. 2003; Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol 84:2305–2315 [View Article][PubMed]
    [Google Scholar]
  38. Tsang K. W., Ho P. L., Ooi G. C., Yee W. K., Wang T., Chan-Yeung M., Lam W. K., Seto W. H., Yam L. Y. et al. 2003; A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348:1977–1985 [View Article][PubMed]
    [Google Scholar]
  39. Uddin S., Sassano A., Deb D. K., Verma A., Majchrzak B., Rahman A., Malik A. B., Fish E. N., Platanias L. C. 2002; Protein kinase C-δ (PKC-δ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem 277:14408–14416 [View Article][PubMed]
    [Google Scholar]
  40. Vantaggiato C., Formentini I., Bondanza A., Bonini C., Naldini L., Brambilla R. 2006; ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially. J Biol 5:14[PubMed] [CrossRef]
    [Google Scholar]
  41. Varfolomeev E., Blankenship J. W., Wayson S. M., Fedorova A. V., Kayagaki N., Garg P., Zobel K., Dynek J. N., Elliott L. O., Wallweber H. J. A. 2007; IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell 131:669–681 [View Article][PubMed]
    [Google Scholar]
  42. Wang J. Y., Lee C. H., Cheng S. L., Chang H. T., Hsu Y. L., Wang H. C., Chu S. H. 2004a; Comparison of the clinical manifestations of severe acute respiratory syndrome and Mycoplasma pneumoniae pneumonia. J Formos Med Assoc 103:894–899[PubMed]
    [Google Scholar]
  43. Wang W. K., Chen S. Y., Liu I. J., Kao C. L., Chen H. L., Chiang B. L., Wang J. T., Sheng W. H., Hsueh P. R. et al. 2004b; Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome. Clin Infect Dis 39:1071–1075 [View Article][PubMed]
    [Google Scholar]
  44. Wong C. K., Lam C. W., Wu A. K., Ip W. K., Lee N. L., Chan I. H., Lit L. C., Hui D. S., Chan M. H. et al. 2004; Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 136:95–103 [View Article][PubMed]
    [Google Scholar]
  45. Yan H., Xiao G., Zhang J., Hu Y., Yuan F., Cole D. K., Zheng C., Gao G. F. 2004; SARS coronavirus induces apoptosis in Vero E6 cells. J Med Virol 73:323–331 [View Article][PubMed]
    [Google Scholar]
  46. Zampieri C. A., Fortin J. F., Nolan G. P., Nabel G. J. 2007; The ERK mitogen-activated protein kinase pathway contributes to Ebola virus glycoprotein-induced cytotoxicity. J Virol 81:1230–1240 [View Article][PubMed]
    [Google Scholar]
  47. Zhao C., Denison C., Huibregtse J. M., Gygi S., Krug R. M. 2005; Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A 102:10200–10205 [View Article][PubMed]
    [Google Scholar]
  48. Ziebuhr J. 2004; Molecular biology of severe acute respiratory syndrome coronavirus. Curr Opin Microbiol 7:412–419 [View Article][PubMed]
    [Google Scholar]
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