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Virology Journal
Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression

Authors: Xingang Xu, Honglei Zhang, Qi Zhang, Jie Dong, Yabing Liang, Yong Huang, Hung-Jen Liu, Dewen Tong

Published in: Virology Journal | Issue 1/2013

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Abstract

Background

Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research.

Methods

The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival.

Results

The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression.

Conclusions

This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.
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Literature
1.
Ducatelle R, Coussement W, Pensaert MB, Debouck P, Hoorens J: In vivo morphogenesis of a new porcine enteric coronavirus, CV 777. Arch Virol 1981, 68: 35-44. 10.1007/BF01315165PubMedCrossRef
2.
Pensaert MB, de Bouck P: A new coronavirus-like particle associated with diarrhea in swine. Arch Virol 1978, 58: 243-247. 10.1007/BF01317606PubMedCrossRef
3.
Hou X-L, Yu L-Y, Liu J: Development and evaluation of enzyme-linked immunosorbent assay based on recombinant nucleocapsid protein for detection of porcine epidemic diarrhea (PEDV) antibodies. Vet Microbiol 2007, 123: 86-92. 10.1016/j.vetmic.2007.02.014PubMedCrossRef
4.
Song D, Park B: Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines. Virus Genes 2012, 44: 167-175. 10.1007/s11262-012-0713-1PubMedCrossRef
5.
Carvajal A, Lanza I, Diego R, Rubio P, Camenes P: Evaluation of a blocking ELISA using monoclonal antibodies for the detection of porcine epidemic diarrhea virus and its antibodies. J Vet Diagn Invest 1995, 7: 60-64. 10.1177/104063879500700109PubMedCrossRef
6.
Wang K, Lu W, Chen J, Xie S, Shi H, Hsu H, Yu W, Xu K, Bian C, Fischer WB, et al.: PEDV ORF3 encodes an ion channel protein and regulates virus production. FEBS Lett 2012, 586: 384-391. 10.1016/j.febslet.2012.01.005PubMedCrossRef
7.
Egberink HF, Ederveen J, Callebaut P, Horzinek MC: Characterization of the structural proteins of porcine epizootic diarrhea virus, strain CV777. Am J Vet Res 1988, 49: 1320-1324.PubMed
8.
Bridgen A, Kocherhans R, Tobler K, Carvajal A, Ackermann M: Further analysis of the genome of porcine epidemic diarrhoea virus. Adv Exp Med Biol 1998, 440: 781-786.PubMedCrossRef
9.
Kocherhans R, Bridgen A, Ackermann M, Tobler K: Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence. Virus Genes 2001, 23: 137-144. 10.1023/A:1011831902219PubMedCrossRef
10.
Locker JK, Rose JK, Horzinek MC, Rottier PJ: Membrane assembly of the triple-spanning coronavirus M protein. Individual transmembrane domains show preferred orientation. J Biol Chem 1992, 267: 21911-21918.PubMed
11.
Yeo SG, Hernandez M, Krell PJ, Nagy EE: Cloning and sequence analysis of the spike gene of porcine epidemic diarrhea virus Chinju99. Virus Genes 2003, 26: 239-246. 10.1023/A:1024443112717PubMedCrossRef
12.
Ortego J, Ceriani JE, Patiño C, Plana J, Enjuanes L: Absence of E protein arrests transmissible gastroenteritis coronavirus maturation in the secretory pathway. Virology 2007, 368: 296-308. 10.1016/j.virol.2007.05.032PubMedCrossRef
13.
Schierack P, Nordhoff M, Pollmann M, Weyrauch KD, Amasheh S, Lodemann U, Jores J, Tachu B, Kleta S, Blikslager A, et al.: Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine. Histochem Cell Biol 2005, 125: 293-305.PubMedCrossRef
14.
Todd DJ, Lee A-H, Glimcher LH: The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008, 8: 663-674. 10.1038/nri2359PubMedCrossRef
15.
16.
Luppi F, Longo AM, de Boer WI, Rabe KF, Hiemstra PS: Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation. Lung Cancer 2007, 56: 25-33. 10.1016/j.lungcan.2006.11.014PubMedCrossRef
17.
Waugh DJ, Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res 2008, 14: 6735-6741. 10.1158/1078-0432.CCR-07-4843PubMedCrossRef
18.
Hong M: Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation. J Biol Chem 2005, 280: 16821-16828. 10.1074/jbc.M413753200PubMedCrossRef
19.
Li J, Ni M, Lee B, Barron E, Hinton DR, Lee AS: The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. Cell Death Differ 2008, 15: 1460-1471. 10.1038/cdd.2008.81PubMedPubMedCentralCrossRef
20.
Quinones QJ, de Ridder GG, Pizzo SV: GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum. Histol Histopathol 2008, 23: 1409-1416.PubMed
21.
Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M: Multiple control of interleukin-8 gene expression. J Leukoc Biol 2002, 72: 847-855.PubMed
22.
Waris G, Tardif KD, Siddiqui A: Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3. Biochem Pharmacol 2002, 64: 1425-1430. 10.1016/S0006-2952(02)01300-XPubMedCrossRef
23.
Fahy BN, Schlieman MG, Mortenson MM, Virudachalam S, Bold RJ: Targeting BCL-2 overexpression in various human malignancies through NF-κB inhibition by the proteasome inhibitor bortezomib. Cancer Chemother Pharmacol 2005, 56: 46-54. 10.1007/s00280-004-0944-5PubMedCrossRef
24.
Ricca A, Biroccio A, Del Bufalo D, Mackay AR, Santoni A, Cippitelli M: Bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells. Int J Cancer 2000, 86: 188-196. 10.1002/(SICI)1097-0215(20000415)86:2<188::AID-IJC7>3.0.CO;2-WPubMedCrossRef
25.
Batsi C, Markopoulou S, Kontargiris E, Charalambous C, Thomas C, Christoforidis S, Kanavaros P, Constantinou AI, Marcu KB, Kolettas E: Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27Kip1-dependent G1/S cell cycle arrest in conjunction with NF-κB activation. Biochem Pharmacol 2009, 78: 33-44. 10.1016/j.bcp.2009.03.017PubMedPubMedCentralCrossRef
26.
Seo M, Nam H-J, Kim S-Y, Juhnn Y-S: Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-κB in H1299 human lung cancer cells. Biochem Biophys Res Commun 2009, 381: 153-158. 10.1016/j.bbrc.2009.01.188PubMedCrossRef
27.
Junwei G, Baoxian L, Lijie T, Yijing L: Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03. Virus Genes 2006, 33: 215-219. 10.1007/s11262-005-0059-zPubMedCrossRef
28.
Chen J, Wang C, Shi H, Qiu HJ, Liu S, Shi D, Zhang X, Feng L: Complete genome sequence of a chinese virulent porcine epidemic diarrhea virus strain. J Virol 2011, 85: 11538-11539. 10.1128/JVI.06024-11PubMedPubMedCentralCrossRef
29.
Park SJ, Kim HK, Song DS, An DJ, Park BK: Complete genome sequences of a korean virulent porcine epidemic diarrhea virus and its attenuated counterpart. J Virol 2012, 86: 5964. 10.1128/JVI.00557-12PubMedPubMedCentralCrossRef
30.
31.
Li Q, Verma IM: NF-κB regulation in the immune system. Nat Rev Immunol 2002, 2: 725-734. 10.1038/nri910PubMedCrossRef
32.
Wietek C, O’Neill LAJ: Diversity and regulation in the NF-κB system. Trends Biochem Sci 2007, 32: 311-319. 10.1016/j.tibs.2007.05.003PubMedCrossRef
33.
Geng H, Wittwer T, Dittrich-Breiholz O, Kracht M, Schmitz ML: Phosphorylation of NF-κB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep 2009, 10: 381-386. 10.1038/embor.2009.10PubMedPubMedCentralCrossRef
34.
Honglei Z, Jie D, Yabing L, Xingang X, Dewen T: RT-PCR identification of porcine epidemic diarrhea virus and sequence analysis of its M, N and E gene. Acta Agriculturae Boreali-occidentalis Sinica 2012, 21: 24-28.
35.
Jing W, Yanming Z, Gang T, Fangning L, Hongchao Z, Lei H, Xiaoyun Y, Yanzhao X, Haixia H: The isolation and identification of neonatal swine intestinal epithelial cells. Acta Veterinaria et Zootechnica Sinica 2010, 41: 92-98.
36.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods 2001, 25: 402-408. 10.1006/meth.2001.1262PubMedCrossRef
37.
Matsuo Y, Sawai H, Ochi N, Yasuda A, Sakamoto M, Takahashi H, Funahashi H, Takeyama H, Guha S: Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking NF-κB activity. Dig Dis Sci 2009, 55: 1167-1176.PubMedCrossRef
Metadata
Title
Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression
Authors
Xingang Xu
Honglei Zhang
Qi Zhang
Jie Dong
Yabing Liang
Yong Huang
Hung-Jen Liu
Dewen Tong
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-26

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