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Licensed Unlicensed Requires Authentication Published by De Gruyter March 5, 2016

Proteasomes raise the microtubule dynamics in influenza A (H1N1) virus-infected LLC-MK2 cells

  • Flora De Conto EMAIL logo , Carlo Chezzi , Alessandra Fazzi , Sergey V. Razin , Maria Cristina Arcangeletti , Maria Cristina Medici , Rita Gatti and Adriana Calderaro

Abstract

The dynamics of microtubule networks are known to have an impact on replication of influenza A virus in some cellular models. Here we present evidence suggesting that at late stages of LLC-MK2 cell infection by influenza A (H1N1) virus the ubiquitin-proteasome protein degradation system participates in destabilization of microtubules, and favours virus replication. Chemical inhibition of proteasome activity partially suppresses influenza A virus replication, while stimulation of proteasome activity favours influenza A virus replication. Conversely, in another cellular model, A549 cells, inhibitors and activators of proteasomes have a small effect on influenza A virus replication. These data suggest that influenza A virus might take selective advantage of proteasome functions in order to set up a favourable cytoskeletal “environment” for its replication and spread. Furthermore, the relationship between influenza virus and the host cell is likely to depend on both the cellular model and the virus strain.

References

1. Alto, N.M. and Orth, K. Subversion of cell signaling by pathogens. Cold Spring Harb. Perspect. Biol. 4 (2012), DOI: 10.1101/cshperspect.a006114.10.1101/cshperspect.a006114Search in Google Scholar PubMed PubMed Central

2. Arcangeletti, M.C., Pinardi, F., Medici, M.C., Pilotti, E., De Conto, F., Ferraglia, F., Landini, M.P., Chezzi, C. and Dettori, G. Cytoskeleton involvement during human cytomegalovirus replicative cycle in human embryo fibroblasts. New Microbiol. 23 (2000) 241-256.Search in Google Scholar

3. Han, X., Li, Z., Chen, H., Wang, H., Mei, L., Wu, S., Zhang, T., Liu, B. and Lin, X. Influenza virus A/Beijing/501/2009(H1N1) NS1 interacts with β-tubulin and induces disruption of the microtubule network and apoptosis on A549 cells. PLoS One 7 (2012), DOI: 10.1371/journal.pone.0048340.10.1371/journal.pone.0048340Search in Google Scholar PubMed PubMed Central

4. Hussein, I.T. and Mir, M.A. How hantaviruses modulate cellular pathways for efficient replication? Front. Biosci. Search in Google Scholar

5 (2013) 154-166. 5. Netherton, C., Moffat, K., Brooks, E. and Wileman, T. A guide to viral inclusions, membrane rearrangements, factories, and viroplasm produced during virus replication. Adv. Virus Res. 70 (2007) 101-182.Search in Google Scholar

6. Wade, R.H. On and around microtubules: an overview. Mol. Biotechnol. 43 (2009) 177-191. DOI: 10.1007/s12033-009-9193-5.10.1007/s12033-009-9193-5Search in Google Scholar PubMed

7. Garnham, C.P. and Roll-Mecak, A. The chemical complexity of cellular microtubules: tubulin post-translational modification enzymes and their roles in tuning microtubule functions. Cytoskeleton 69 (2012) 442-463. DOI: 10.1002/cm.21027.10.1002/cm.21027Search in Google Scholar PubMed PubMed Central

8. Lundin, V.F., Leroux, M.R. and Stirling, P.C. Quality control of cytoskeletal proteins and human disease. Trends Biochem. Sci. 35 (2010) 288-297. DOI: 10.1016/j.tibs.2009.Search in Google Scholar

9. Greber, U.F. and Way, M. A superhighway to virus infection. Cell 124 (2006) 741-754.Search in Google Scholar

10. Liu, C., Liu, M. and Zhou, J. Analysis of microtubule-mediated intracellular viral transport. Methods Mol. Med. 137 (2007) 175-180.Search in Google Scholar

11. Brice, A. and Moseley, G.W. Viral interactions with microtubules: orchestrators of host cell biology? Future Virol. 8 (2013) 229-243.DOI: 10.2217/fvl.12.137.10.2217/fvl.12.137Search in Google Scholar

12. De Conto, F., Di Lonardo, E., Arcangeletti, M.C., Chezzi, C., Medici, M.C. and Calderaro, A. Highly dynamic microtubules improve the effectiveness of early stages of human influenza A/NWS/33 virus infection in LLC-MK2 cells. PLoS One 7 (2012). DOI: 10.1371/journal.pone.0041207.10.1371/journal.pone.0041207Search in Google Scholar PubMed PubMed Central

13. Aprea, S., Del Valle, L., Mameli, G., Sawaya, B.E., Khalili, K. and Peruzzi, F. Tubulin-mediated binding of human immunodeficiency virus-1 Tat to the cytoskeleton causes proteasomal-dependent degradation of microtubuleassociated protein 2 and neuronal damage. J. Neurosci. 26 (2006) 4054-4062.Search in Google Scholar

14. Haqshenas, G. The p7 protein of hepatitis C virus is degraded via the proteasome-dependent pathway. Virus Res. 176 (2013) 211-215. DOI: 10.1016/j.virusres.2013.06.009.10.1016/j.virusres.2013.06.009Search in Google Scholar PubMed

15. Ko, N.L., Taylor, J.M., Bellon, M., Bai, X.T., Shevtsov, S.P., Dundr, M. and Nicot, C. PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency. Blood 121 (2013) 791-800. DOI: 10.1182/blood-2012-03-420414.10.1182/blood-2012-03-420414Search in Google Scholar PubMed PubMed Central

16. Schmidt, F.I., Bleck, C.K., Reh, L., Novy, K., Wollscheid, B., Helenius, A., Stahlberg, H. and Mercer, J. Vaccinia virus entry is followed by core activation and proteasome-mediated release of the immunomodulatory effector VH1 from lateral bodies. Cell Rep. 4 (2013) 464-476. DOI: 10.1016/j.celrep.2013.06.028.10.1016/j.celrep.2013.06.028Search in Google Scholar PubMed

17. Schneider, M., Ackermann, K., Stuart, M., Wex, C., Protzer, U., Schätzl, H.M. and Gilch, S. Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain. J. Virol. 86 (2012) 10112-10122. DOI: 10.1128/JVI.01001-12. 10.1128/JVI.01001-12Search in Google Scholar PubMed PubMed Central

18. Blanchette, P. and Branton, P.E. Manipulation of the ubiquitin-proteasome pathway by small DNA tumor viruses. Virology 384 (2009) 317-323. DOI: 10.1016/j.virol.2008.10.005.10.1016/j.virol.2008.10.005Search in Google Scholar

19. Hu, Z., Zhang, Z., Doo, E., Coux, O., Goldberg, A.L. and Liang, T.J. Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome complex. J. Virol. 73 (1999) 7231-7240.Search in Google Scholar

20. Sherry, B. Rotavirus and reovirus modulation of the interferon response. J. Interferon Cytokine Res. 29 (2009) 559-567. DOI: 10.1089/jir.2009.0072.10.1089/jir.2009.0072Search in Google Scholar

21. Khor, R., McElroy, L.J. and Whittaker, G.R. The ubiquitin-vacuolar protein sorting system is selectively required during entry of influenza virus into host cells. Traffic 4 (2003) 857-868.Search in Google Scholar

22. Widjaja, I., de Vries, E., Tscherne, D.M., García-Sastre, A., Rottier, P.J. and de Haan, C.A. Inhibition of the ubiquitin-proteasome system affects influenza A virus infection at a postfusion step. J. Virol. 84 (2010) 9625-9631. DOI: 10.1128/JVI.01048-10.10.1128/JVI.01048-10Search in Google Scholar

23. Coux, O., Tanaka, K. and Goldberg, A.L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65 (1996) 801-847.Search in Google Scholar

24. Reinstein, E. and Ciechanover, A. Narrative review: protein degradation and human diseases: the ubiquitin connection. Ann. Intern. Med. 145 (2006) 676-684.Search in Google Scholar

25. Tanaka, K., Mizushima, T. and Saeki, Y. The proteasome: molecular machinery and pathophysiological roles. Biol. Chem. 393 (2012) 217-234. DOI: 10.1515/hsz-2011-0285.10.1515/hsz-2011-0285Search in Google Scholar

26. Arcangeletti, M.C., De Conto, F., Ferraglia, F., Pinardi, F., Gatti, R., Orlandini, G., Covan, S., Motta, F., Rodighiero, I., Dettori, G. and Chezzi, C. Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus. Arch. Virol. 153 (2008) 1209-1221. DOI: 10.1007/s00705-008-0103-0.10.1007/s00705-008-0103-0Search in Google Scholar

27. De Conto, F., Covan, S., Arcangeletti, M.C., Orlandini, G., Gatti, R., Dettori, G. and Chezzi, C. Differential infectious entry of human influenza A/NWS/33 virus (H1N1) in mammalian kidney cells. Virus Res. 155 (2011) 221-230. DOI: 10.1016/j.virusres.2010.10.008.10.1016/j.virusres.2010.10.008Search in Google Scholar

28. Lee, B.H., Lee M.J., Park, S., Oh, D.C., Elsasser, S., Chen, P.C., Gartner, C., Dimora, N., Hanna, J., Gygi, S.P., Wilson, S.M., King, R.W. and Finley, D. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467 (2010) 179-184. DOI: 10.1038/nature09299.10.1038/nature09299Search in Google Scholar

29. Poruchynsky, M.S., Sackett, D.L., Robey, R.W., Ward, Y., Annunziata, C. and Fojo, T. Proteasome inhibitors increase tubulin polymerization and stabilization in tissue culture cells: a possible mechanism contributing to peripheral neuropathy and cellular toxicity following proteasome inhibition. Cell Cycle 7 (2008) 940-949.Search in Google Scholar

30. Downing, K.H. Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics. Annu. Rev. Cell Dev. Biol. 16 (2000) 89-111. Search in Google Scholar

31. Drewes, G., Ebneth, A. and Mandelkow, E.M. MAPs, MARKs and microtubule dynamics. Trends Biochem. Sci. 23 (1998) 307-311.10.1016/S0968-0004(98)01245-6Search in Google Scholar

32. Westermann, S. and Weber, K. Post-translational modifications regulate microtubule function. Nat. Rev. Mol. Cell Biol. 4 (2003) 938-947.Search in Google Scholar

33. Kamemura, K., Ito, A., Shimazu, T., Matsuyama, A., Maeda, S., Yao, T.P., Horinouchi, S., Khochbin, S. and Yoshida, M. Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells. Biochem. Biophys. Res. Commun. 374 (2008) 84-89. DOI: 10.1016/ j.bbrc.2008.06.092.Search in Google Scholar

34. Zhang, S., Zhang, Q.C. and Jiang, S.J. Effect of trichostatin A and paclitaxel on the proliferation and apoptosis of lung adenocarcinoma cells. Chin. Med. J. 126 (2013) 129-134.Search in Google Scholar

35. Sommi, P., Necchi, V., Vitali, A., Montagna, D., De Luigi, A., Salmona, M., Ricci, V. and Solcia, E. PaCS is a novel cytoplasmic structure containing functional proteasome and inducible by cytokines/trophic factors. PLoS One 8 (2013), DOI: 10.1371/journal.pone.0082560.10.1371/journal.pone.0082560Search in Google Scholar PubMed PubMed Central

36. Souza Lda, C., Camargo, R., Demasi, M., Santana, J.M., de Sá, C.M. and de Freitas, S.M. Effects of an anticarcinogenic Bowman-Birk protease inhibitor on purified 20S proteasome and MCF-7 breast cancer cells. PLoS One 9 (2014), DOI: 10.1371/journal.pone.0086600.10.1371/journal.pone.0086600Search in Google Scholar PubMed PubMed Central

37. David, D.C., Layfield, R., Serpell, L., Narain, Y., Goedert, M. and Spillantini, M.G. Proteasomal degradation of tau protein. J. Neurochem. 83 (2002) 176-185.Search in Google Scholar

38. Peth, A., Boettcher, J.P. and Dubiel, W. Ubiquitin-dependent proteolysis of the microtubule end-binding protein 1, EB1, is controlled by the COP9 signalosome: possible consequences for microtubule filament stability. J. Mol. Biol. 368 (2007) 550-563.Search in Google Scholar

39. Jouvenet, N. and Wileman, T. African swine fever virus infection disrupts centrosome assembly and function. J. Gen. Virol. 86 (2005) 589-594.Search in Google Scholar

40. Martin, D., Duarte, M., Lepault, J. and Poncet, D. Sequestration of free tubulin molecules by the viral protein NSP2 induces microtubule depolymerization during rotavirus infection. J. Virol. 84 (2010) 2522-2532. DOI: 10.1128/JVI.01883-09.10.1128/JVI.01883-09Search in Google Scholar PubMed PubMed Central

41. Simon, K.O., Whitaker-Dowling, P.A., Youngner, J.S. and Widnell, C.C. Sequential disassembly of the cytoskeleton in BHK21 cells infected with vesicular stomatitis virus. Virology 177 (1990) 289-297.Search in Google Scholar

42. Rock, K.L., Gramm, C., Rothstein, L., Clark, K., Stein, R., Dick, L., Hwang, D. and Goldberg, A.L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78 (1994) 761-771.Search in Google Scholar

43. Fiedler, M.A., Wernke-Dollries, K. and Stark, J.M. Inhibition of TNF-alphainduced NF-kappaB activation and IL-8 release in A549 cells with the proteasome inhibitor MG-132. Am. J. Respir. Cell Mol. Biol. 19 (1998) 259-268. Search in Google Scholar

44. Jang, B.C., Lim, K.J., Paik, J.H., Kwon, Y.K., Shin, S.W., Kim, S.C., Jung, T.Y., Kwon, T.K., Cho, J.W., Baek, W.K., Kim, S.P., Suh, M.H. and Suh, S.I. Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB. Biochem. Biophys. Res. Commun. 320 (2004) 1026-1033.10.1016/j.bbrc.2004.06.049Search in Google Scholar PubMed

45. Watanabe, H., Tanaka, Y., Shimazu, Y., Sugahara, F., Kuwayama, M., Hiramatsu, A., Kiyotani, K., Yoshida, T. and Sakaguchi, T. Cell-specific inhibition of paramyxovirus maturation by proteasome inhibitors. Microbiol. Immunol. 49 (2005) 835-844.Search in Google Scholar

46. Park, S.W., Han, M.G., Park, C., Ju, Y.R., Ahn, B.Y. and Ryou, J. Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation. J. Gen. Virol. 94 (2013) 2424-2428. DOI: 10.1099/vir.0.054312-0.10.1099/vir.0.054312-0Search in Google Scholar PubMed PubMed Central

47. Agholme, L., Nath, S., Domert, J., Marcusson, J., Kågedal, K. and Hallbeck, M. Proteasome inhibition induces stress kinase dependent transport deficitsimplications for Alzheimer's disease. Mol. Cell Neurosci. 58 (2014) 29-39. DOI: 10.1016/j.mcn.2013.11.001.10.1016/j.mcn.2013.11.001Search in Google Scholar PubMed

48. Diaz-Corrales, F.J., Miyazaki, I., Asanuma, M., Ruano, D. and Rios, R.M. Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT. Neurobiol. Aging 33 (2012) 2462-2477. DOI: 10.1016/j.neurobiolaging.2011.11.014.10.1016/j.neurobiolaging.2011.11.014Search in Google Scholar PubMed

49. Staff, N.P., Podratz, J.L., Grassner, L., Bader, M., Paz, J., Knight, A.M., Loprinzi, C.L., Trushina, E. and Windebank, A.J. Bortezomib alters microtubule polymerization and axonal transport in rat dorsal root ganglion neurons. Neurotoxicology 39 (2013) 124-131. DOI: 10.1016/j.neuro.2013.09.001.10.1016/j.neuro.2013.09.001Search in Google Scholar PubMed PubMed Central

50. Husain, M. and Harrod, K.S. Enhanced acetylation of alpha-tubulin in influenza A virus infected epithelial cells. FEBS Lett. 585 (2011) 128-132. DOI: 10.1016/j.febslet.2010.11.023.10.1016/j.febslet.2010.11.023Search in Google Scholar PubMed

51. Chiang, H.S., Zhao, Y., Song, J.H., Liu, S., Wang, N., Terhorst, C., Sharpe, A.H., Basavappa, M., Jeffrey, K.L. and Reinecker, H.C. GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses. Nat. Immunol. 5 (2014) 63-71. DOI: 10.1038/ni.2766.10.1038/ni.2766Search in Google Scholar PubMed PubMed Central

52. Garoufalis, E., Kwan, I., Lin, R., Mustafa, A., Pepin, N., Roulston, A., Lacoste, J. and Hiscott, J. Viral induction of the human beta interferon promoter: modulation of transcription by NF-kappa B/rel proteins and interferon regulatory factors. J. Virol. 68 (1994) 4707-4715.Search in Google Scholar

53. Ronni, T., Matikainen, S., Sareneva, T., Melen, K., Pirhonen, J., Keskinen, P. and Julkunen, I. Regulation of IFN-alpha/beta, MxA, 2’,5’-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells. J. Immunol. 158 (1997) 2363-2374.Search in Google Scholar

54. Wurzer, W.J., Ehrhardt, C., Pleschka, S., Berberich-Siebelt, F., Wolff, T., Walczak, H., Planz, O. and Ludwig, S. NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J. Biol. Chem. 279 (2004) 30931-30937.Search in Google Scholar

55. Karin, M. and Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 18 (2000) 621-663.10.1146/annurev.immunol.18.1.621Search in Google Scholar PubMed

56. An, J., Sun, Y., Fisher, M. and Rettig, M.B. Maximal apoptosis of renal cell carcinoma by the proteasome inhibitor bortezomib is nuclear factor-kappaB dependent. Mol. Cancer Ther. 3 (2004) 727-736.Search in Google Scholar

57. Fujioka, S., Sclabas, G.M., Schmidt, C., Frederick, W.A., Dong, Q.G., Abbruzzese, J.L., Evans, D.B., Baker, C. and Chiao, P.J. Function of nuclear factor kB in pancreatic cancer metastasis. Clin. Cancer Res. 9 (2003) 346-354.Search in Google Scholar

58. Pham, L.V., Tamayo, A.T., Yoshimura, L.C., Lo, P. and Ford, R.J. Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J. Immunol. 171 (2003) 88-95.Search in Google Scholar

59. Dudek, S.E, Luig, C., Pauli, E.K., Schubert, U., Ludwig, S. The clinically approved proteasome inhibitor PS-341 efficiently blocks influenza A virus and vesicular stomatitis virus propagation by establishing an antiviral state. J. Virol. 84 (2010) 9439-9451. DOI: 10.1128/JVI.00533-10.10.1128/JVI.00533-10Search in Google Scholar PubMed PubMed Central

60. Pyo, C.W., Shin, N., Jung, K.I., Choi, J.H., Choi, S.Y. Alteration of copperzinc superoxide dismutase 1 expression by influenza A virus is correlated with virus replication. Biochem. Biophys. Res. Commun. 450 (2014) 711-716. DOI:10.1016/j.bbrc.2014.06.037.10.1016/j.bbrc.2014.06.037Search in Google Scholar PubMed

61. Imai, Y., Kuba, K., Neely, G.G., Yaghubian-Malhami, R., Perkmann, T., van Loo, G., Ermolaeva, M., Veldhuizen, R., Leung, Y.H., Wang, H., Liu, H., Sun, Y., Pasparakis, M., Kopf, M., Mech, C., Bavari, S., Peiris, J.S., Slutsky, A.S., Akira, S., Hultqvist, M., Holmdahl, R., Nicholls, J., Jiang, C., Binder, C.J. and Penninger, J.M. Identification of oxidative stress and Tolllike receptor 4 signaling as a key pathway of acute lung injury. Cell 133 (2008) 235-249. DOI: 10.1016/j.cell.2008.02.043.10.1016/j.cell.2008.02.043Search in Google Scholar PubMed PubMed Central

62. Vlahos, R., Stambas, J., Bozinovski, S., Broughton, B.R., Drummond, G.R., Selemidis, S. Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog. 7 (2011):e1001271. DOI: 10.1371/journal.ppat.1001271. 10.1371/journal.ppat.1001271Search in Google Scholar PubMed PubMed Central

Received: 2015-6-26
Accepted: 2015-11-4
Published Online: 2016-3-5
Published in Print: 2015-12-1

© University of Wroclaw, Poland

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