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Archives of Virology

, Volume 157, Issue 6, pp 1011–1018 | Cite as

Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication

  • Chunchun Meng
  • Zhizhi Zhou
  • Ke Jiang
  • Shengqing Yu
  • Lijun Jia
  • Yantao Wu
  • Yanqing Liu
  • Songshu Meng
  • Chan Ding
Original Article

Abstract

Newcastle disease virus (NDV) can replicate in tumor cells and induce apoptosis in late stages of infection. However, the interaction between NDV and cells in early stages of infection is not well understood. Here, we report that, shortly after infection, NDV triggers the formation of autophagosomes in U251 glioma cells, as demonstrated by an increased number of double-membrane vesicles, GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) a dot formations, and elevated production of LC3II. Moreover, modulation of NDV-induced autophagy by rapamycin, chloroquine or small interfering RNAs targeting the genes critical for autophagosome formation (Atg5 and Beclin-1) affects virus production, indicating that autophagy may be utilized by NDV to facilitate its own production. Furthermore, the class III phosphatidylinositol 3-kinase (PI3K)/Beclin-1 pathway plays a role in NDV-induced autophagy and virus production. Collectively, our data provide a unique example of a paramyxovirus that uses autophagy to enhance its production.

Keywords

Rapamycin U251 Cell Newcastle Disease Virus Virus Production Autophagosome Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was funded by Special Fund for Agro-scientific Research in the Public Interest (201003012), National High-tech R and D Program (863 Program, 2011AA10A209) and State Key Laboratory of Veterinary Biotechnology of China (SKLVBF201109).

References

  1. 1.
    Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ (2001) Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett 172:27–36CrossRefPubMedGoogle Scholar
  2. 2.
    Terman A, Dalen H, Eaton JW, Neuzil J, Brunk UT (2003) Mitochondrial recycling and aging of cardiac myocytes: the role of autophagocytosis. Exp Gerontol 38:863–876CrossRefPubMedGoogle Scholar
  3. 3.
    Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A (2002) DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol 157:455–468CrossRefPubMedGoogle Scholar
  4. 4.
    Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688CrossRefPubMedGoogle Scholar
  5. 5.
    Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728CrossRefPubMedGoogle Scholar
  6. 6.
    Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4:151–175PubMedGoogle Scholar
  7. 7.
    Dreux M, Chisari FV (2010) Viruses and the autophagy machinery. Cell Cycle 9:1295–1307CrossRefPubMedGoogle Scholar
  8. 8.
    He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93CrossRefPubMedGoogle Scholar
  9. 9.
    Meijer AJ, Codogno P (2004) Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36:2445–2462CrossRefPubMedGoogle Scholar
  10. 10.
    Schmid D, Munz C (2007) Innate and adaptive immunity through autophagy. Immunity 27:11–21CrossRefPubMedGoogle Scholar
  11. 11.
    Deretic V (2009) Strange bedfellows expose ancient secrets of autophagy in immunity. Immunity 30:479–481CrossRefPubMedGoogle Scholar
  12. 12.
    Orvedahl A, Levine B (2008) Autophagy and viral neurovirulence. Cell Microbiol 10:1747–1756CrossRefPubMedGoogle Scholar
  13. 13.
    Wong J, Zhang J, Si X, Gao G, Mao I, McManus BM (2008) Autophagosome supports coxsackievirus B3 replication in host cells. J Virol 82:9143–9153CrossRefPubMedGoogle Scholar
  14. 14.
    Lee YR, Lei HY, Liu MT, Wang JR, Chen SH, Jiang-Shieh YF (2008) Autophagic machinery activated by dengue virus enhances virus replication. Virology 374:240–248CrossRefPubMedGoogle Scholar
  15. 15.
    Jackson WT, Giddings TH Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR (2005) Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3:e156CrossRefPubMedGoogle Scholar
  16. 16.
    Manuse MJ, Briggs CM, Parks GD (2010) Replication-independent activation of human plasmacytoid dendritic cells by the paramyxovirus SV5 Requires TLR7 and autophagy pathways. Virology 405:383–389CrossRefPubMedGoogle Scholar
  17. 17.
    Joubert PE, Meiffren G, Gregoire IP, Pontini G, Richetta C, Flacher M (2009) Autophagy induction by the pathogen receptor CD46. Cell Host Microbe 6:354–366CrossRefPubMedGoogle Scholar
  18. 18.
    Zanetti F, Berinstein A, Pereda A, Taboga O, Carrillo E (2005) Molecular characterization and phylogenetic analysis of NDV isolates from healthy wild birds. Avian Dis 49:546–550CrossRefPubMedGoogle Scholar
  19. 19.
    Bian JC, Wang K, Kong XG, Liu HR, Chen F, Hu MZ (2011) Caspase and p38 MAPK-dependent apoptotic induction in A549 lung cancer cells by Newcastle disease virus. Arch Virol 156:1335–1344CrossRefPubMedGoogle Scholar
  20. 20.
    Meng S, Gui Q, Xu Q, Lu K, Jiao X, Fan J (2010) Association of Shp2 with phosphorylated IL-22R1 is required for interleukin-22-induced MAP kinase activation. J Mol Cell Biol 2:223–230CrossRefPubMedGoogle Scholar
  21. 21.
    Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z (2010) LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J 29:1792–1802CrossRefPubMedGoogle Scholar
  22. 22.
    Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518CrossRefPubMedGoogle Scholar
  23. 23.
    Takeuchi H, Kondo Y, Fujiwara K, Kanzawa T, Aoki H, Mills GB (2005) Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res 65:3336–3346PubMedGoogle Scholar
  24. 24.
    Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502CrossRefPubMedGoogle Scholar
  25. 25.
    Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (2001) Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep 2:330–335CrossRefPubMedGoogle Scholar
  26. 26.
    Li J, Qin Z, Liang Z (2009) The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells. BMC Cancer 9:215CrossRefPubMedGoogle Scholar
  27. 27.
    Park CM, Park MJ, Kwak HJ, Lee HC, Kim MS, Lee SH (2006) Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 66:8511–8519CrossRefPubMedGoogle Scholar
  28. 28.
    Jiang H, Shang X, Wu H, Gautam SC, Al-Holou S, Li C (2009) Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells. J Exp Ther Oncol 8:25–33PubMedGoogle Scholar
  29. 29.
    Zhang H, Kong X, Kang J, Su J, Li Y, Zhong J (2009) Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci 110:376–388CrossRefPubMedGoogle Scholar
  30. 30.
    Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25:1025–1040CrossRefPubMedGoogle Scholar
  31. 31.
    Solomon VR, Lee H (2009) Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol 625:220–233CrossRefPubMedGoogle Scholar
  32. 32.
    Geng Y, Kohli L, Klocke BJ, Roth KA (2010) Chloroquine-induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent. Neuro Oncol 12:473–481PubMedGoogle Scholar
  33. 33.
    Shacka JJ, Klocke BJ, Shibata M, Uchiyama Y, Datta G, Schmidt RE (2006) Bafilomycin A1 inhibits chloroquine-induced death of cerebellar granule neurons. Mol Pharmacol 69:1125–1136CrossRefPubMedGoogle Scholar
  34. 34.
    Nemoto T, Tanida I, Tanida-Miyake E, Minematsu-Ikeguchi N, Yokota M, Ohsumi M (2003) The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification. J Biol Chem 278:39517–39526CrossRefPubMedGoogle Scholar
  35. 35.
    Belov GA, Altan-Bonnet N, Kovtunovych G, Jackson CL, Lippincott-Schwartz J, Ehrenfeld E (2007) Hijacking components of the cellular secretory pathway for replication of poliovirus RNA. J Virol 81:558–567CrossRefPubMedGoogle Scholar
  36. 36.
    Kemball CC, Alirezaei M, Flynn CT, Wood MR, Harkins S, Kiosses WB (2010) Coxsackievirus infection induces autophagy-like vesicles and megaphagosomes in pancreatic acinar cells in vivo. J Virol 84:12110–12124CrossRefPubMedGoogle Scholar
  37. 37.
    Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–1401CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Chunchun Meng
    • 1
  • Zhizhi Zhou
    • 2
  • Ke Jiang
    • 3
  • Shengqing Yu
    • 1
  • Lijun Jia
    • 4
  • Yantao Wu
    • 3
  • Yanqing Liu
    • 2
  • Songshu Meng
    • 2
  • Chan Ding
    • 1
  1. 1.Shanghai Veterinary Research InstituteThe Chinese Academy of Agricultural SciencesShanghaiPeople’s Republic of China
  2. 2.College of Bioscience and BiotechnologyYangzhou UniversityYangzhouPeople’s Republic of China
  3. 3.College of Veterinary MedicineYangzhou UniversityYangzhouPeople’s Republic of China
  4. 4.Department of Immunology, Shanghai Medical CollegeFudan UniversityShanghaiPeople’s Republic of China

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