1887

Abstract

Dynamin2 is a large GTPase that regulates vesicle trafficking, and the GTPase activity of dynamin2 is required for the multistep process of adenovirus infection. Activity of dynamin2 may be regulated by post-translational phosphorylation and -nitrosylation modifications. In this study, we demonstrate a role for dynamin2 -nitrosylation in adenovirus infection of epithelial cells. We show that adenovirus serotype 5 (Ad5) infection augments production of nitric oxide (NO) in epithelial cells and causes the -nitrosylation of dynamin2, mainly on cysteine 86 (C86) and 607 (C607) residues. Forced overexpression of dynamin2 bearing C86A and/or C607A mutations decreases Ad5 infection. Diminishing NO synthesis by RNAi-induced knockdown of endogenous endothelial NO synthase (eNOS) expression attenuates virus infection of target cells. Ad5 infection promotes the kinetically dynamic -nitrosylation of dynamin2 and eNOS: there is a rapid decrease in eNOS -nitrosylation and a concomitant increase in the dynamin2 -nitrosylation. These results support the hypothesis that dynamin2 -nitrosylation following eNOS activation facilitates adenovirus infection of host epithelial cells.

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2012-10-01
2024-12-07
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References

  1. Ahn S., Maudsley S., Luttrell L. M., Lefkowitz R. J., Daaka Y. 1999; Src-mediated tyrosine phosphorylation of dynamin is required for β2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J Biol Chem 274:1185–1188 [View Article][PubMed]
    [Google Scholar]
  2. Ahn S., Kim J., Lucaveche C. L., Reedy M. C., Luttrell L. M., Lefkowitz R. J., Daaka Y. 2002; Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor. J Biol Chem 277:26642–26651 [View Article][PubMed]
    [Google Scholar]
  3. Bauer P. M., Fulton D., Boo Y. C., Sorescu G. P., Kemp B. E., Jo H., Sessa W. C. 2003; Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric-oxide synthase. J Biol Chem 278:14841–14849 [View Article][PubMed]
    [Google Scholar]
  4. Ben-Israel H., Kleinberger T. 2002; Adenovirus and cell cycle control. Front Biosci 7:d1369–d1395 [View Article][PubMed]
    [Google Scholar]
  5. Bergelson J. M., Cunningham J. A., Droguett G., Kurt-Jones E. A., Krithivas A., Hong J. S., Horwitz M. S., Crowell R. L., Finberg R. W. 1997; Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320–1323 [View Article][PubMed]
    [Google Scholar]
  6. Berk A. J. 1986; Adenovirus promoters and E1A transactivation. Annu Rev Genet 20:45–77 [View Article][PubMed]
    [Google Scholar]
  7. Cao S., Yao J., McCabe T. J., Yao Q., Katusic Z. S., Sessa W. C., Shah V. 2001; Direct interaction between endothelial nitric-oxide synthase and dynamin-2. Implications for nitric-oxide synthase function. J Biol Chem 276:14249–14256[PubMed]
    [Google Scholar]
  8. Chen Z. P., Mitchelhill K. I., Michell B. J., Stapleton D., Rodriguez-Crespo I., Witters L. A., Power D. A., Ortiz de Montellano P. R., Kemp B. E. 1999; AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 443:285–289 [View Article][PubMed]
    [Google Scholar]
  9. Conner S. D., Schmid S. L. 2003; Regulated portals of entry into the cell. Nature 422:37–44 [View Article][PubMed]
    [Google Scholar]
  10. de Jong R. N., van der Vliet P. C., Brenkman A. B. 2003; Adenovirus DNA replication: protein priming, jumping back and the role of the DNA binding protein DBP. Curr Top Microbiol Immunol 272:187–211[PubMed]
    [Google Scholar]
  11. Dudzinski D. M., Igarashi J., Greif D., Michel T. 2006; The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol 46:235–276 [View Article][PubMed]
    [Google Scholar]
  12. Durieux A. C., Prudhon B., Guicheney P., Bitoun M. 2010; Dynamin 2 and human diseases. J Mol Med (Berl) 88:339–350 [View Article][PubMed]
    [Google Scholar]
  13. Echavarría M. 2008; Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 21:704–715 [View Article][PubMed]
    [Google Scholar]
  14. Erwin P. A., Lin A. J., Golan D. E., Michel T. 2005; Receptor-regulated dynamic S-nitrosylation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem 280:19888–19894 [View Article][PubMed]
    [Google Scholar]
  15. Fish K. N., Schmid S. L., Damke H. 2000; Evidence that dynamin-2 functions as a signal-transducing GTPase. Mol Biol Cell 11:1141
    [Google Scholar]
  16. Fulton D., Gratton J. P., McCabe T. J., Fontana J., Fujio Y., Walsh K., Franke T. F., Papapetropoulos A., Sessa W. C. 1999; Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399:597–601 [View Article][PubMed]
    [Google Scholar]
  17. Fulton D., Gratton J. P., Sessa W. C. 2001; Post-translational control of endothelial nitric oxide synthase: why isn’t calcium/calmodulin enough?. J Pharmacol Exp Ther 299:818–824[PubMed]
    [Google Scholar]
  18. Gastaldelli M., Imelli N., Boucke K., Amstutz B., Meier O., Greber U. F. 2008; Infectious adenovirus type 2 transport through early but not late endosomes. Traffic 9:2265–2278 [View Article][PubMed]
    [Google Scholar]
  19. Greber U. F., Willetts M., Webster P., Helenius A. 1993; Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75:477–486 [View Article][PubMed]
    [Google Scholar]
  20. Heeringa P., van Goor H., Moshage H., Klok P. A., Huitema M. G., de Jager A., Schep A. J., Kallenberg C. G. M. 1998; Expression of iNOS, eNOS, and peroxynitrite-modified proteins in experimental anti-myeloperoxidase associated crescentic glomerulonephritis. Kidney Int 53:382–393 [View Article][PubMed]
    [Google Scholar]
  21. Kang-Decker N., Cao S., Chatterjee S., Yao J., Egan L. J., Semela D., Mukhopadhyay D., Shah V. 2007; Nitric oxide promotes endothelial cell survival signaling through S-nitrosylation and activation of dynamin-2. J Cell Sci 120:492–501 [View Article][PubMed]
    [Google Scholar]
  22. Kennedy M. A., Parks R. J. 2009; Adenovirus virion stability and the viral genome: size matters. Mol Ther 17:1664–1666 [View Article][PubMed]
    [Google Scholar]
  23. Kojima H., Nakatsubo N., Kikuchi K., Kawahara S., Kirino Y., Nagoshi H., Hirata Y., Nagano T. 1998; Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem 70:2446–2453 [View Article][PubMed]
    [Google Scholar]
  24. Kornberg M. D., Sen N., Hara M. R., Juluri K. R., Nguyen J. V. K., Snowman A. M., Law L., Hester L. D., Snyder S. H. 2010; GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol 12:1094–1100 [View Article][PubMed]
    [Google Scholar]
  25. Lynch J. P. III, Fishbein M., Echavarria M. 2011; Adenovirus. Semin Respir Crit Care Med 32:494–511 [View Article][PubMed]
    [Google Scholar]
  26. McConnell M. J., Imperiale M. J. 2004; Biology of adenovirus and its use as a vector for gene therapy. Hum Gene Ther 15:1022–1033 [View Article][PubMed]
    [Google Scholar]
  27. Meier O., Greber U. F. 2004; Adenovirus endocytosis. J Gene Med 6:Suppl 1S152–S163 [View Article][PubMed]
    [Google Scholar]
  28. Michell B. J., Chen Zp, Tiganis T., Stapleton D., Katsis F., Power D. A., Sim A. T., Kemp B. E. 2001; Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276:17625–17628 [View Article][PubMed]
    [Google Scholar]
  29. Mooren O. L., Kotova T. I., Moore A. J., Schafer D. A. 2009; Dynamin2 GTPase and cortactin remodel actin filaments. J Biol Chem 284:23995–24005 [View Article][PubMed]
    [Google Scholar]
  30. Nakamura T., Wang L., Wong C. C. L., Scott F. L., Eckelman B. P., Han X. M., Tzitzilonis C., Meng F. J., Gu Z. Z.other authors 2010; Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell 39:184–195 [View Article][PubMed]
    [Google Scholar]
  31. Nakatsubo N., Kojima H., Kikuchi K., Nagoshi H., Hirata Y., Maeda D., Imai Y., Irimura T., Nagano T. 1998; Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: diaminofluoresceins. FEBS Lett 427:263–266 [View Article][PubMed]
    [Google Scholar]
  32. Nemerow G. R., Stewart P. L. 1999; Role of α(v) integrins in adenovirus cell entry and gene delivery. Microbiol Mol Biol Rev 63:725–734[PubMed]
    [Google Scholar]
  33. Praefcke G. J. K., McMahon H. T. 2004; The dynamin superfamily: universal membrane tubulation and fission molecules?. Nat Rev Mol Cell Biol 5:133–147 [View Article][PubMed]
    [Google Scholar]
  34. Rajala M. S., Rajala R. V. S., Astley R. A., Butt A. L., Chodosh J. 2005; Corneal cell survival in adenovirus type 19 infection requires phosphoinositide 3-kinase/Akt activation. J Virol 79:12332–12341 [View Article][PubMed]
    [Google Scholar]
  35. Ravi K., Brennan L. A., Levic S., Ross P. A., Black S. M. 2004; S-nitrosylation of endothelial nitric oxide synthase is associated with monomerization and decreased enzyme activity. Proc Natl Acad Sci U S A 101:2619–2624 [View Article][PubMed]
    [Google Scholar]
  36. Sanlioglu S., Benson P. K., Yang J. S., Atkinson E. M., Reynolds T., Engelhardt J. F. 2000; Endocytosis and nuclear trafficking of adeno-associated virus type 2 are controlled by rac1 and phosphatidylinositol-3 kinase activation. J Virol 74:9184–9196 [View Article][PubMed]
    [Google Scholar]
  37. Suomalainen M., Nakano M. Y., Boucke K., Keller S., Greber U. F. 2001; Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear targeting of virus. EMBO J 20:1310–1319 [View Article][PubMed]
    [Google Scholar]
  38. Tanabe K., Takei K. 2009; Dynamic instability of microtubules requires dynamin 2 and is impaired in a Charcot-Marie-Tooth mutant. J Cell Biol 185:939–948 [View Article][PubMed]
    [Google Scholar]
  39. Vellinga J., Rabelink M. J., Cramer S. J., van den Wollenberg D. J., Van der Meulen H., Leppard K. N., Fallaux F. J., Hoeben R. C. 2004; Spacers increase the accessibility of peptide ligands linked to the carboxyl terminus of adenovirus minor capsid protein IX. J Virol 78:3470–3479 [View Article][PubMed]
    [Google Scholar]
  40. Vigne E., Mahfouz I., Dedieu J. F., Brie A., Perricaudet M., Yeh P. 1999; RGD inclusion in the hexon monomer provides adenovirus type 5-based vectors with a fiber knob-independent pathway for infection. J Virol 73:5156–5161[PubMed]
    [Google Scholar]
  41. Wang K. N., Huang S., Kapoor-Munshi A., Nemerow G. 1998; Adenovirus internalization and infection require dynamin. J Virol 72:3455–3458[PubMed]
    [Google Scholar]
  42. Wang G. F., Moniri N. H., Ozawa K., Stamler J. S., Daaka Y. 2006; Nitric oxide regulates endocytosis by S-nitrosylation of dynamin. Proc Natl Acad Sci U S A 103:1295–1300 [View Article][PubMed]
    [Google Scholar]
  43. Wang Z. M., Humphrey C., Frilot N., Wang G. F., Nie Z. Z., Moniri N. H., Daaka Y. 2011; Dynamin2- and endothelial nitric oxide synthase-regulated invasion of bladder epithelial cells by uropathogenic Escherichia coli. J Cell Biol 192:101–110 [View Article][PubMed]
    [Google Scholar]
  44. Wickham T. J., Mathias P., Cheresh D. A., Nemerow G. R. 1993; Integrins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment. Cell 73:309–319 [View Article][PubMed]
    [Google Scholar]
  45. Zsengellér Z. K., Ross G. F., Trapnell B. C., Szabó C., Whitsett J. A. 2001; Adenovirus infection increases iNOS and peroxynitrite production in the lung. Am J Physiol Lung Cell Mol Physiol 280:L503–L511[PubMed]
    [Google Scholar]
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