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
2021-03-07
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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 σ A 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 σ A and σ NS 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 σ A 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- κ B-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 σ C 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 σ A of avian reovirus S1133. Virology 293:379–385 [CrossRef]
    [Google Scholar]
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