1887

Abstract

Stimulated by energetic stress, AMP-activated protein kinase (AMPK) controls several cellular functions. It was discovered here that infection of Vero cells with avian reovirus (ARV) upregulated AMPK and mitogen-activated protein kinase (MAPK) p38 phosphorylation in a time- and dose-dependent manner. Being an energy status sensor, AMPK is potentially an upstream regulator of MAPK p38. Treatment with 5-amino-4-imidazolecarboxamide ribose (AICAR), a well-known activator of AMPK, induced phosphorylation of MAPK p38. Unlike AICAR, wortmannin or rapamycin did not induce phosphorylation of MAPK p38, suggesting that mTOR inhibition is not a determining factor in MAPK p38 phosphorylation. Inhibition of AMPK by compound C antagonized the effect of AICAR on MAPK p38 in Vero cells. Specific inhibition of AMPK by small interfering RNA or compound C also suppressed ARV-induced phosphorylation of MAPK kinase (MKK) 3/6 and MAPK p38 in Vero and DF-1 cells, thereby providing a link between AMPK signalling and the MAPK p38 pathway. The mechanism of ARV-enhanced phosphorylation of MKK 3/6 and MAPK p38 in cells was not merely due to glucose deprivation, a probable activator of AMPK. In the current study, direct inhibition of MAPK p38 by SB202190 decreased the level of ARV-induced syncytium formation in Vero and DF-1 cells, and decreased the protein levels of ARV A and C and the progeny titre of ARV, suggesting that activation of MAPK p38 is beneficial for ARV replication. Taken together, these results suggested that AMPK could facilitate MKK 3/6 and MAPK p38 signalling that is beneficial for ARV replication. Although well studied in energy metabolism, this study provides evidence for the first time that AMPK plays a role in modulating ARV and host-cell interaction.

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2009-12-01
2019-11-21
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References

  1. Banerjee, S., Narayanan, K., Mizutani, T. & Makino, S. ( 2002; ). Murine coronavirus replication-induced p38 mitogen-activated protein kinase activation promotes interleukin-6 production and virus replication in cultured cells. J Virol 76, 5937–5948.[CrossRef]
    [Google Scholar]
  2. Benavente, J. & Martínez-Costas, J. ( 2007; ). Avian reovirus: structure and biology. Virus Res 123, 105–119.[CrossRef]
    [Google Scholar]
  3. Beretta, L., Gingras, A. C., Svitkin, Y. V., Hall, M. N. & Sonenberg, N. ( 1996; ). Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J 15, 658–664.
    [Google Scholar]
  4. Bodelón, G., Labrada, L., Martínez-Costas, J. & Benavente, J. ( 2002; ). Modification of late membrane permeability in avian reovirus-infected cells. J Biol Chem 277, 17789–17796.[CrossRef]
    [Google Scholar]
  5. Eliopoulos, A. G., Gallagher, N. J., Blake, S. M. S., Dawson, C. W. & Young, L. S. ( 1999; ). Activation of the p38 mitogen-activated protein kinase pathway by Epstein–Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production. J Biol Chem 274, 16085–16096.[CrossRef]
    [Google Scholar]
  6. Feng, Z., Zhang, H., Levine, A. J. & Jin, S. ( 2005; ). The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A 102, 8204–8209.[CrossRef]
    [Google Scholar]
  7. Gaidhu, M. P., Fediuc, S. & Ceddia, R. B. ( 2006; ). AICAR-induced AMPK phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. J Biol Chem 281, 25956–25964.[CrossRef]
    [Google Scholar]
  8. Gleason, C. E., Lu, D., Witters, L. A., Newgard, C. B. & Birnbaum, M. J. ( 2007; ). The role of AMPK and mTOR in nutrient sensing in pancreatic β-cells. J Biol Chem 282, 10341–10351.[CrossRef]
    [Google Scholar]
  9. González-López, C., Martínez-Costas, J., Esteban, M. & Benavente, J. ( 2003; ). Evidence that avian reovirus σA protein is an inhibitor of the double-stranded RNA-dependent protein kinase. J Gen Virol 84, 1629–1639.[CrossRef]
    [Google Scholar]
  10. Hay, N. & Sonenberg, N. ( 2004; ). Upstream and downstream of mTOR. Genes Dev 18, 1926–1945.[CrossRef]
    [Google Scholar]
  11. 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]
  12. Hsu, C. J., Wang, C. Y., Lee, L. H., Shih, W. L., Chang, C. I., Cheng, H. L., Chulu, J. L. C., Ji, W. T. & Liu, H. J. ( 2006; ). Development and characterization of monoclonal antibodies against reovirus sigma C protein and their application in detection of reovirus isolates. Avian Pathol 35, 320–326.[CrossRef]
    [Google Scholar]
  13. Huang, P. H., Li, Y. J., Su, Y. P., Lee, L. H. & Liu, H. J. ( 2005; ). Epitope mapping and functional analysis of σA and σNS proteins of avian reovirus. Virology 332, 584–595.[CrossRef]
    [Google Scholar]
  14. Iglesias, M. A., Furler, S. M., Cooney, G. J., Kraegen, E. W. & Ye, J. M. ( 2004; ). AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo. Diabetes 53, 1649–1654.[CrossRef]
    [Google Scholar]
  15. Ji, W. T., Wang, L., Lin, R. C., Huang, W. R. & Liu, H. J. ( 2009; ). Avian reovirus influences phosphorylation of several factors involved in host protein translation including eukaryotic translation elongation factor 2 (eEF2) in Vero cells. Biochem Biophys Res Commun 384, 301–305.[CrossRef]
    [Google Scholar]
  16. Johnson, G. L. & Lapadat, R. ( 2002; ). Mitogen-acitvated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911–1912.[CrossRef]
    [Google Scholar]
  17. Jung, S. N., Yang, W. K., Kim, J., Kim, H. S., Kim, E. J., Yun, H., Park, H., Kim, S. S., Choe, W. & other authors ( 2008; ). Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells. Carcinogenesis 29, 713–721.[CrossRef]
    [Google Scholar]
  18. Kimura, N., Tokunaga, C., Dalal, S., Richardson, C., Yoshino, K., Hara, K., Kemp, B. E., Witters, L. A., Mimura, O. & Yonezawa, K. ( 2003; ). A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. Genes Cells 8, 65–79.[CrossRef]
    [Google Scholar]
  19. Kudchodkar, S. B., Del Prete, G. Q., Maguire, T. G. & Alwine, J. C. ( 2007; ). AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early times of human cytomegalovirus infection. J Virol 81, 3649–3651.[CrossRef]
    [Google Scholar]
  20. Liu, H. J., Lin, P. Y., Wang, L. R., Hsu, H. Y., Liao, M. H. & Shih, W. L. ( 2008; ). Activation of small GTPase RhoA and Rac1 is required for avian reovirus p10-induced syncytium formation. Mol Cells 26, 396–403.
    [Google Scholar]
  21. Martínez-Costas, J., Grande, A., Varela, R., García-Martínez, C. & Benavente, J. ( 1997; ). Protein architecture of avian reovirus S1133 and identification of the cell attachment protein. J Virol 71, 59–64.
    [Google Scholar]
  22. Martínez-Costas, J., González-López, C., Vakharia, V. N. & Benavente, J. ( 2000; ). Possible involvement of the double-stranded RNA-binding core protein σA in the resistance of avian reovirus to interferon. J Virol 74, 1124–1131.[CrossRef]
    [Google Scholar]
  23. Meusel, T. R. & Imani, F. ( 2003; ). Viral induction of inflammatory cytokines in human epithelial cells follows a p38 mitogen-activated protein kinase-dependent but NF-κB-independent pathway. J Immunol 171, 3768–3774.[CrossRef]
    [Google Scholar]
  24. Norman, K. L., Hirasawa, K., Yang, A. D., Shields, M. A. & Lee, P. W. K. ( 2004; ). Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection. Proc Natl Acad Sci U S A 101, 11099–11104.[CrossRef]
    [Google Scholar]
  25. Pelletier, A., Joly, E., Prentki, M. & Coderre, L. ( 2005; ). Adenosine 5′-monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes. Endocrinology 146, 2285–2294.[CrossRef]
    [Google Scholar]
  26. Pencek, R. R., Shearer, J., Camacho, R. C., James, F. D., Lacy, D. B., Fueger, P. T., Donahue, E. P., Snead, W. & Wasserman, D. H. ( 2005; ). 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside causes acute hepatic insulin resistance in vivo. Diabetes 54, 355–360.[CrossRef]
    [Google Scholar]
  27. Rutter, G. A., Silver Xavier, G. & Leclerc, I. ( 2003; ). Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem J 375, 1–16.[CrossRef]
    [Google Scholar]
  28. Saha, A. K., Persons, K., Safer, J. D., Luo, Z., Holick, M. F. & Ruderman, N. B. ( 2006; ). AMPK regulation of the growth of cultured human keratinocytes. Biochem Biophys Res Commun 349, 519–524.[CrossRef]
    [Google Scholar]
  29. Shapiro, L., Heidenreich, K. A., Meintzer, M. K. & Dinarello, C. A. ( 1998; ). Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro. Proc Natl Acad Sci U S A 95, 7422–7426.[CrossRef]
    [Google Scholar]
  30. Shih, W. L., Hsu, H. W., Liao, M. H., Lee, L. H. & Liu, H. J. ( 2004; ). Avian reovirus σC protein induces apoptosis in cultured cells. Virology 321, 65–74.[CrossRef]
    [Google Scholar]
  31. Smith, A. C., Bruce, C. R. & Dyck, D. J. ( 2005; ). AMP kinase activation with AICAR further increases fatty acid oxidation and blunts triacylglycerol hydrolysis in contracting rat soleus muscle. J Physiol 565, 547–553.[CrossRef]
    [Google Scholar]
  32. Tzatsos, A. & Tsichlis, P. N. ( 2007; ). Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794. J Biol Chem 282, 18069–18082.[CrossRef]
    [Google Scholar]
  33. Viollet, B., Foretz, M., Guigas, B., Horman, S., Dentin, R., Bertrand, L., Hue, L. & Andreelli, F. ( 2006; ). Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 574, 41–53.[CrossRef]
    [Google Scholar]
  34. Xi, X., Han, J. & Zhang, J. Z. ( 2001; ). Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase. J Biol Chem 276, 41029–41034.[CrossRef]
    [Google Scholar]
  35. Yin, H. S., Su, Y. P. & Lee, L. H. ( 2002; ). Evidence of nucleotidyl phosphatase activity associated with core protein σA of avian reovirus S1133. Virology 293, 379–385.[CrossRef]
    [Google Scholar]
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