Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Online
ISSN
1689-1392
See all formats and pricing
More options …
Volume 20, Issue 5

Issues

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

Flora De Conto / Carlo Chezzi / Alessandra Fazzi / Sergey V. Razin
  • Institute of Gene Biology, Russian Academy of Sciences and Lomonosow Moscow State University, Moscow, Russia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maria Cristina Arcangeletti / Maria Cristina Medici / Rita Gatti
  • Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Adriana Calderaro
Published Online: 2016-03-05 | DOI: https://doi.org/10.1515/cmble-2015-0052

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.

Keywords: Influenza A virus; Microtubule cytoskeleton; Viral nucleoprotein; Virus-host interaction; Proteasomes; Acetylated alpha-tubulin; Microtubuleassociated protein 4; Gene expression; MG132; IU1

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.CrossrefGoogle Scholar

  • 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.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.CrossrefGoogle Scholar

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

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

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

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

  • 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.CrossrefGoogle 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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. CrossrefGoogle Scholar

  • 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle 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.CrossrefGoogle 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.CrossrefGoogle Scholar

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

  • 31. Drewes, G., Ebneth, A. and Mandelkow, E.M. MAPs, MARKs and microtubule dynamics. Trends Biochem. Sci. 23 (1998) 307-311.CrossrefGoogle Scholar

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

  • 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.Google Scholar

  • 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle Scholar

  • 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.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.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. 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.Google Scholar

  • 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.CrossrefGoogle 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.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.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.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.CrossrefGoogle Scholar

  • 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.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.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.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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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. CrossrefGoogle Scholar

About the article

Received: 2015-06-26

Accepted: 2015-11-04

Published Online: 2016-03-05

Published in Print: 2015-12-01


Citation Information: Cellular and Molecular Biology Letters, Volume 20, Issue 5, Pages 840–866, ISSN (Online) 1689-1392, DOI: https://doi.org/10.1515/cmble-2015-0052.

Export Citation

© University of Wroclaw, Poland. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Flora De Conto, Alessandra Fazzi, Sergey V. Razin, Maria Cristina Arcangeletti, Maria Cristina Medici, Silvana Belletti, Carlo Chezzi, and Adriana Calderaro
Molecular and Cellular Biochemistry, 2017

Comments (0)

Please log in or register to comment.
Log in