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Critical role of eukaryotic elongation factor 1 alpha 1 (EEF1A1) in avian reovirus sigma-C-induced apoptosis and inhibition of viral growth

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Abstract

Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth and malabsorption syndrome. It is well established that the ARV sigma-C protein induces apoptosis in host cells. However, the underlying molecular mechanism of this induction is still unclear. We report here the identification of eukaryotic elongation factor 1 alpha 1 (EEF1A1) as the interacting partner of σC. We found that σC-induced apoptosis in DF-1 cells could be completely abolished by knockdown of EEF1A1 by siRNA. Furthermore, knockdown of EEF1A1 markedly reduced ARV-induced apoptosis associated with decreased caspase-9 and -3 activation and cytochrome C release, leading to increased ARV growth in host cells. Thus, EEF1A1 plays a critical role in σC-induced apoptosis and inhibition of viral growth.

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Abbreviations

ARV:

Avian reovirus

EEF1A1:

Eukaryotic elongation factor 1 alpha 1

RNAi:

RNA interference

References

  1. Varela R, Martinez-Costas J, Mallo M, Benavente J (1996) Intracellular posttranslational modifications of S1133 avian reovirus proteins. J Virol 70(5):2974–2981

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Labrada L, Bodelon G, Vinuela J, Benavente J (2002) Avian reoviruses cause apoptosis in cultured cells: viral uncoating, but not viral gene expression, is required for apoptosis induction. J Virol 76(16):7932–7941

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Benavente J, Martinez-Costas J (2007) Avian reovirus: structure and biology. Virus Res 123(2):105–119

    Article  CAS  PubMed  Google Scholar 

  4. Varela R, Benavente J (1994) Protein coding assignment of avian reovirus strain S1133. J Virol 68(10):6775–6777

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Schnitzer TJ, Ramos T, Gouvea V (1982) Avian reovirus polypeptides: analysis of intracellular virus-specified products, virions, top component, and cores. J Virol 43(3):1006–1014

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Bodelon G, Labrada L, Martinez-Costas J, Benavente J (2001) The avian reovirus genome segment S1 is a functionally tricistronic gene that expresses one structural and two nonstructural proteins in infected cells. Virology 290(2):181–191

    Article  CAS  PubMed  Google Scholar 

  7. Shmulevitz M, Yameen Z, Dawe S et al (2002) Sequential partially overlapping gene arrangement in the tricistronic S1 genome segments of avian reovirus and Nelson Bay reovirus: implications for translation initiation. J Virol 76(2):609–618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Clarke P, Tyler KL (2003) Reovirus-induced apoptosis: a minireview. Apoptosis 8(2):141–150

    Article  CAS  PubMed  Google Scholar 

  9. Coffey CM, Sheh A, Kim IS, Chandran K, Nibert ML, Parker JS (2006) Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. J Virol 80(17):8422–8438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Shih WL, Hsu HW, Liao MH, Lee LH, Liu HJ (2004) Avian reovirus sigmaC protein induces apoptosis in cultured cells. Virology 321(1):65–74

    Article  CAS  PubMed  Google Scholar 

  11. Barry C, Duncan R (2009) Multifaceted sequence-dependent and -independent roles for reovirus FAST protein cytoplasmic tails in fusion pore formation and syncytiogenesis. J Virol 83(23):12185–12195

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Top D, Barry C, Racine T, Ellis CL, Duncan R (2009) Enhanced fusion pore expansion mediated by the trans-acting Endodomain of the reovirus FAST proteins. PLoS Pathog 5(3):e1000331

    Article  PubMed Central  PubMed  Google Scholar 

  13. Salsman J, Top D, Boutilier J, Duncan R (2005) Extensive syncytium formation mediated by the reovirus FAST proteins triggers apoptosis-induced membrane instability. J Virol 79(13):8090–8100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Shmulevitz M, Corcoran J, Salsman J, Duncan R (2004) Cell-cell fusion induced by the avian reovirus membrane fusion protein is regulated by protein degradation. J Virol 78(11):5996–6004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Lin PY, Liu HJ, Liao MH et al (2010) Activation of PI 3-kinase/Akt/NF-kappaB and Stat3 signaling by avian reovirus S1133 in the early stages of infection results in an inflammatory response and delayed apoptosis. Virology 400(1):104–114

    Article  CAS  PubMed  Google Scholar 

  16. Connolly JL, Rodgers SE, Clarke P et al (2000) Reovirus-induced apoptosis requires activation of transcription factor NF-kappaB. J Virol 74(7):2981–2989

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Lin PY, Lee JW, Liao MH et al (2009) Modulation of p53 by mitogen-activated protein kinase pathways and protein kinase C delta during avian reovirus S1133-induced apoptosis. Virology 385(2):323–334

    Article  CAS  PubMed  Google Scholar 

  18. Liu HJ, Lin PY, Lee JW, Hsu HY, Shih WL (2005) Retardation of cell growth by avian reovirus p17 through the activation of p53 pathway. Biochem Biophys Res Commun 336(2):709–715

    Article  CAS  PubMed  Google Scholar 

  19. Chulu JL, Lee LH, Lee YC et al (2007) Apoptosis induction by avian reovirus through p53 and mitochondria-mediated pathway. Biochem Biophys Res Commun 356(3):529–535

    Article  CAS  PubMed  Google Scholar 

  20. Geng H, Zhang Y, Liu-Partanen Y et al (2009) Apoptosis induced by duck reovirus p10.8 protein in primary duck embryonated fibroblast and Vero E6 cells. Avian Dis 53(3):434–440

    Article  PubMed  Google Scholar 

  21. Lin PY, Liu HJ, Chang CD et al (2011) Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens. Arch Virol 156(11):1917–1929

    Article  CAS  PubMed  Google Scholar 

  22. Ping-Yuan L, Hung-Jen L, Meng-Jiun L et al (2006) Avian reovirus activates a novel proapoptotic signal by linking Src to p53. Apoptosis 11(12):2179–2193

    Article  PubMed  Google Scholar 

  23. Uma R, Kataria M, Rahul S, Kataria JM (2013) Anti-neoplastic effect of avian reovirus sigma C protein on Rous sarcoma virus-induced tumors in chicken. Acta Virol 57(1):69–74

    Article  CAS  PubMed  Google Scholar 

  24. Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Epidemiol 27:493–497

    Google Scholar 

  25. Chen E, Proestou G, Bourbeau D, Wang E (2000) Rapid up-regulation of peptide elongation factor EF-1alpha protein levels is an immediate early event during oxidative stress-induced apoptosis. Exp Cell Res 259(1):140–148

    Article  CAS  PubMed  Google Scholar 

  26. Duttaroy A, Bourbeau D, Wang XL, Wang E (1998) Apoptosis rate can be accelerated or decelerated by overexpression or reduction of the level of elongation factor-1 alpha. Exp Cell Res 238(1):168–176

    Article  CAS  PubMed  Google Scholar 

  27. Talapatra S, Wagner JD, Thompson CB (2002) Elongation factor-1 alpha is a selective regulator of growth factor withdrawal and ER stress-induced apoptosis. Cell Death Differ 9(8):856–861

    Article  CAS  PubMed  Google Scholar 

  28. Mateyak MK, Kinzy TG (2010) eEF1A: thinking outside the ribosome. J Biol Chem 258(28):21209–21213

    Article  Google Scholar 

  29. Li Z, Wang Y, Xue Y, Li X, Cao H, Zheng SJ (2012) Critical role for voltage-dependent anion channel 2 in infectious bursal disease virus-induced apoptosis in host cells via interaction with VP5. J Virol 86(3):1328–1338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Wei L, Hou L, Zhu S, Wang J, Zhou J, Liu J (2011) Infectious bursal disease virus activates the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway by interaction of VP5 protein with the p85alpha subunit of PI3K. Virology 417(1):211–220

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez-Grille J, Busch LK, Martinez-Costas J, Benavente J (2014) Avian reovirus-triggered apoptosis enhances both virus spread and the processing of the viral nonstructural muNS protein. Virology 462–463:49–59

    Article  PubMed  Google Scholar 

  32. Hsu HW, Su HY, Huang PH, Lee BL, Liu HJ (2005) Sequence and phylogenetic analysis of P10- and P17-encoding genes of avian reovirus. Avian Dis 49(1):36–42

    Article  PubMed  Google Scholar 

  33. Liu HJ, Huang PH (2001) Sequence and phylogenetic analysis of the sigmaA-encoding gene of avian reovirus. J Virol Methods 98(2):99–107

    Article  CAS  PubMed  Google Scholar 

  34. Liu HJ, Lee LH, Hsu HW, Kuo LC, Liao MH (2003) Molecular evolution of avian reovirus: evidence for genetic diversity and reassortment of the S-class genome segments and multiple cocirculating lineages. Virology 314(1):336–349

    Article  CAS  PubMed  Google Scholar 

  35. Su YP, Su BS, Shien JH, Liu HJ, Lee LH (2006) The sequence and phylogenetic analysis of avian reovirus genome segments M1, M2, and M3 encoding the minor core protein muA, the major outer capsid protein muB, and the nonstructural protein muNS. J Virol Methods 133(2):146–157

    Article  CAS  PubMed  Google Scholar 

  36. Gouvea VS, Schnitzer TJ (1982) Polymorphism of the genomic RNAs among the avian reoviruses. J Gen Virol 61(Pt l):87–91

  37. Gouvea VS, Schnitzer TJ (1982) Polymorphism of the migration of double-stranded RNA genome segments of avian reoviruses. J Virol 43(2):465–471

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Hsu CJ, Wang CY, Lee LH et al (2006) Development and characterization of monoclonal antibodies against avian reovirus sigma C protein and their application in detection of avian reovirus isolates. Avian Pathol 35(4):320–326

    Article  CAS  PubMed  Google Scholar 

  39. Lin HY, Chuang ST, Chen YT, Shih WL, Chang CD, Liu HJ (2007) Avian reovirus-induced apoptosis related to tissue injury. Avian Pathol 36(2):155–159

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jingliang Su for his kind assistance. This work was supported by grants from the National Natural Science Foundation of China (# 31272543 and 31430085) and Earmarked Fund for Modern Agro-Industry Technology Research System (#NYCYTX-41).

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Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China

    Zhiqiang Zhang, Wencheng Lin, Xiaoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

  2. Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, China Agricultural University, Beijing, 100193, China

    Zhiqiang Zhang, Wencheng Lin, Xiaoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

  3. College of Veterinary Medicine, China Agricultural University, 2 Yuan-Ming-Yuan West Road, Beijing, 100193, China

    Zhiqiang Zhang, Wencheng Lin, Xiaoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

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  1. Zhiqiang Zhang
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  2. Wencheng Lin
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  3. Xiaoqi Li
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  4. Hong Cao
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Correspondence to Yongqiang Wang or Shijun J. Zheng.

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Zhang, Z., Lin, W., Li, X. et al. Critical role of eukaryotic elongation factor 1 alpha 1 (EEF1A1) in avian reovirus sigma-C-induced apoptosis and inhibition of viral growth. Arch Virol 160, 1449–1461 (2015). https://doi.org/10.1007/s00705-015-2403-5

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  • DOI: https://doi.org/10.1007/s00705-015-2403-5

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