Early Pattern of Epstein-Barr Virus Infection in Gastric Epithelial Cells by “Cell-in-cell”
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摘要
Epstein-Barr virus(EBV) is an important human dsDNA virus, which has been shown to be associated with several malignancies including about 10% of gastric carcinomas. How EBV enters an epithelial cell has been an interesting project for investigation. ‘‘Cell-in-cell'' infection was recently reported an efficient way for the entry of EBV into nasopharynx epithelial cells. The present approach was to explore the feasibility of this mode for EBV infection in gastric epithelial cells and the dynamic change of host inflammatory reaction. The EBV-positive lymphoblastic cells of Akata containing a GFP tag in the viral genome were co-cultured with the gastric epithelial cells(GES-1). The infection situation was observed under fluorescence and electron microscopies. Real-time quantitative PCR and Western-blotting assay were employed to detect the expression of a few specific cytokines and inflammatory factors. The results demonstrated that EBV could get into gastric epithelial cells by ‘‘cell-in-cell'' infection but not fully successful due to the host fighting. IL-1 b, IL-6 and IL-8 played prominent roles in the cellular response to the infection. The activation of NF-j B and HSP70 was also required for the host antiviral response. The results imply that the gastric epithelial cells could powerfully resist the virus invader via cell-in-cell at the early stage through inflammatory and innate immune responses.
Epstein-Barr virus(EBV) is an important human dsDNA virus, which has been shown to be associated with several malignancies including about 10% of gastric carcinomas. How EBV enters an epithelial cell has been an interesting project for investigation. ‘‘Cell-in-cell'' infection was recently reported an efficient way for the entry of EBV into nasopharynx epithelial cells. The present approach was to explore the feasibility of this mode for EBV infection in gastric epithelial cells and the dynamic change of host inflammatory reaction. The EBV-positive lymphoblastic cells of Akata containing a GFP tag in the viral genome were co-cultured with the gastric epithelial cells(GES-1). The infection situation was observed under fluorescence and electron microscopies. Real-time quantitative PCR and Western-blotting assay were employed to detect the expression of a few specific cytokines and inflammatory factors. The results demonstrated that EBV could get into gastric epithelial cells by ‘‘cell-in-cell'' infection but not fully successful due to the host fighting. IL-1 b, IL-6 and IL-8 played prominent roles in the cellular response to the infection. The activation of NF-j B and HSP70 was also required for the host antiviral response. The results imply that the gastric epithelial cells could powerfully resist the virus invader via cell-in-cell at the early stage through inflammatory and innate immune responses.
Epstein-Barr virus(EBV) is an important human dsDNA virus, which has been shown to be associated with several malignancies including about 10% of gastric carcinomas. How EBV enters an epithelial cell has been an interesting project for investigation. ‘‘Cell-in-cell'' infection was recently reported an efficient way for the entry of EBV into nasopharynx epithelial cells. The present approach was to explore the feasibility of this mode for EBV infection in gastric epithelial cells and the dynamic change of host inflammatory reaction. The EBV-positive lymphoblastic cells of Akata containing a GFP tag in the viral genome were co-cultured with the gastric epithelial cells(GES-1). The infection situation was observed under fluorescence and electron microscopies. Real-time quantitative PCR and Western-blotting assay were employed to detect the expression of a few specific cytokines and inflammatory factors. The results demonstrated that EBV could get into gastric epithelial cells by ‘‘cell-in-cell'' infection but not fully successful due to the host fighting. IL-1 b, IL-6 and IL-8 played prominent roles in the cellular response to the infection. The activation of NF-j B and HSP70 was also required for the host antiviral response. The results imply that the gastric epithelial cells could powerfully resist the virus invader via cell-in-cell at the early stage through inflammatory and innate immune responses.
引文
Arora N,Alsaied O,Dauer P,Majumder K,Modi S,Giri B,Dudeja V,Banerjee S,Von Hoff D,Saluja A(2017)Downregulation of sp1 by minnelide leads to decrease in hsp70 and decrease in tumor burden of gastric cancer.PLoS ONE 12:e0171827
Bornkamm GW,Behrends U,Mautner J(2006)The infectious kiss:newly infected b cells deliver epstein-barr virus to epithelial cells.Proc Natl Acad Sci USA 103:7201-7202
Chakravorty M,Ghosh A,Choudhury A,Santra A,Hembrum J,Roychoudhury S(2004)Ethnic differences in allele distribution for the il8 and il1b genes in populations from eastern india.Hum Biol 76:153-159
Chen L,Yuan W,Chen Z,Wu S,Ge J,Chen J,Chen Z(2015)Vasoactive intestinal peptide represses activation of tumorassociated macrophages in gastric cancer via regulation of tnfalpha,il-6,il-12 and inos.Int J Oncol 47:1361-1370
Chen J,Sathiyamoorthy K,Zhang X,Schaller S,Perez White BE,Jardetzky TS,Longnecker R(2018)Ephrin receptor a2 is a functional entry receptor for epstein-barr virus.Nat Microbiol3:172-180
Choi SR,Lee SA,Kim YJ,Ok CY,Lee HJ,Hahm KB(2009)Role of heat shock proteins in gastric inflammation and ulcer healing.J Physiol Pharmacol 60:5-17
Chong JM,Sakuma K,Sudo M,Osawa T,Ohara E,Uozaki H,Shibahara J,Kuroiwa K,Tominaga S,Hippo Y,Aburatani H,Funata N,Fukayama M(2002)Interleukin-1beta expression in human gastric carcinoma with epstein-barr virus infection.J Virol 76:6825-6831
Cohen JI,Fauci AS,Varmus H,Nabel GJ(2011)Epstein-barr virus:an important vaccine target for cancer prevention.Sci Transl Med 3:107fs107
Dehne N,Fuhrmann D,Brune B(2013)Hypoxia-inducible factor(hif)in hormone signaling during health and disease.Cardiovasc Hematol Agents Med Chem 11:125-135
Ding L,Li L,Yang J,Zhou S,Li W,Tang M,Shi Y,Yi W,Cao Y(2007)Latent membrane protein 1 encoded by epstein-barr virus induces telomerase activity via p16ink4a/rb/e2f1 and jnk signaling pathways.J Med Virol 79:1153-1163
Ding Y,Li XR,Yang KY,Huang LH,Hu G,Gao K(2013)Proteomics analysis of gastric epithelial ags cells infected with epstein-barr virus.Asian Pac J Cancer Prev 14:367-372
Gambhir S,Vyas D,Hollis M,Aekka A,Vyas A(2015)Nuclear factor kappa b role in inflammation associated gastrointestinal malignancies.World J Gastroenterol 21:3174-3183
Henle G,Henle W,Clifford P,Diehl V,Kafuko GW,Kirya BG,Klein G,Morrow RH,Munube GM,Pike P,Tukei PM,Ziegler JL(1969)Antibodies to epstein-barr virus in burkitt’s lymphoma and control groups.J Natl Cancer Inst 43:1147-1157
Hu TZ,Huang LH,Xu CX,Liu XM,Wang Y,Xiao J,Zhou L,Luo L,Jiang XX(2015)Expressional profiles of transcription factors in the progression of helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis.Med Oncol 32:265
Hwang YS,Jeong M,Park JS,Kim MH,Lee DB,Shin BA,Mukaida N,Ellis LM,Kim HR,Ahn BW,Jung YD(2004)Interleukin-1beta stimulates il-8 expression through map kinase and ros signaling in human gastric carcinoma cells.Oncogene23:6603-6611
Lee HW,Lee EH,Kim SH,Roh MS,Jung SB,Choi YC(2013)Heat shock protein 70(hsp70)expression is associated with poor prognosis in intestinal type gastric cancer.Virchows Arch463:489-495
Li L,Zhang Y,Guo BB,Chan FK,Tao Q(2014)Oncogenic induction of cellular high cpg methylation by epstein-barr virus in malignant epithelial cells.Chin J Cancer 33:604-608
Li Y,Long X,Huang L,Yang M,Yuan Y,Wang Y,Delecluse HJ,Kuang E(2016)Epstein-barr virus bzlf1-mediated downregulation of proinflammatory factors is essential for optimal lytic viral replication.J Virol 90:887-903
Lian S,Xia Y,Ung TT,Khoi PN,Yoon HJ,Kim NH,Kim KK,Jung YD(2016)Carbon monoxide releasing molecule-2 ameliorates il-1beta-induced il-8 in human gastric cancer cells.Toxicology361-362:24-38
Liu L,Zhou Q,Xie Y,Zuo L,Zhu F,Lu J(2017)Extracellular vesicles:novel vehicles in herpesvirus infection.Virol Sin32:349-356
Lu JH,Tang YL,Yu HB,Zhou JH,Fu CY,Zeng X,Yu ZY,Yin HL,Wu MH,Zhang JY,Li XL,Li GY(2010)Epstein-barr virus facilitates the malignant potential of immortalized epithelial cells:from latent genome to viral production and maintenance.Lab Invest 90:196-209
Lu Y,Qin Z,Wang J,Zheng X,Lu J,Zhang X,Wei L,Peng Q,Zheng Y,Ou C,Ye Q,Xiong W,Li G,Fu Y,Yan Q,Ma J(2017)Epstein-barr virus mir-bart6-3p inhibits the rig-i pathway.J Innate Immun 9:574-586
Ludigs K,Parfenov V,Du Pasquier RA,Guarda G(2012)Type i ifnmediated regulation of il-1 production in inflammatory disorders.Cell Mol Life Sci 69:3395-3418
Matsusaka K,Funata S,Fukayama M,Kaneda A(2014)DNAmethylation in gastric cancer,related to helicobacter pylori and epstein-barr virus.World J Gastroenterol 20:3916-3926
McColl SR,Roberge CJ,Larochelle B,Gosselin J(1997)EBVinduces the production and release of il-8 and macrophage inflammatory protein-1 alpha in human neutrophils.J Immunol159:6164-6168
McIlwain DR,Berger T,Mak TW(2013)Caspase functions in cell death and disease.Cold Spring Harb Perspect Biol 5:a008656
Morales-Sanchez A,Fuentes-Panana EM(2014)Human viruses and cancer.Viruses 6:4047-4079
Murata T,Tsurumi T(2014)Switching of EBV cycles between latent and lytic states.Rev Med Virol 24:142-153
Nemerow GR,Mold C,Schwend VK,Tollefson V,Cooper NR(1987)Identification of gp350 as the viral glycoprotein mediating attachment of epstein-barr virus(ebv)to the ebv/c3d receptor of b cells:sequence homology of gp350 and c3complement fragment c3d.J Virol 61:1416-1420
Nemerow GR,Houghten RA,Moore MD,Cooper NR(1989)Identification of an epitope in the major envelope protein of epstein-barr virus that mediates viral binding to the b lymphocyte ebv receptor(cr2).Cell 56:369-377
Ni C,Chen Y,Zeng M,Pei R,Du Y,Tang L,Wang M,Hu Y,Zhu H,He M,Wei X,Wang S,Ning X,Wang M,Wang J,Ma L,Chen X,Sun Q,Tang H,Wang Y,Wang X(2015)In-cell infection:a novel pathway for epstein-barr virus infection mediated by cellin-cell structures.Cell Res 25:785-800
Overholtzer M,Mailleux AA,Mouneimne G,Normand G,Schnitt SJ,King RW,Cibas ES,Brugge JS(2007)A nonapoptotic cell death process,entosis,that occurs by cell-in-cell invasion.Cell131:966-979
Pereira ER,Frudd K,Awad W,Hendershot LM(2014)Endoplasmic reticulum(er)stress and hypoxia response pathways interact to potentiate hypoxia-inducible factor 1(hif-1)transcriptional activity on targets like vascular endothelial growth factor(vegf).J Biol Chem 289:3352-3364
Queiroz DM,Rocha AM,Melo FF,Rocha GA,Teixeira KN,Carvalho SD,Bittencourt PF,Castro LP,Crabtree JE(2013)Increased gastric il-1beta concentration and iron deficiency parameters in h.Pylori infected children.PLoS One 8:e57420
Savitri E,Haryana MS(2015)Expression of interleukin-8,interleukin-10 and epstein-barr viral-load as prognostic indicator in nasopharyngeal carcinoma.Glob J Health Sci 7:364-372
Shannon-Lowe CD,Neuhierl B,Baldwin G,Rickinson AB,Delecluse HJ(2006)Resting b cells as a transfer vehicle for epstein-barr virus infection of epithelial cells.Proc Natl Acad Sci USA103:7065-7070
Shinozaki-Ushiku A,Kunita A,Fukayama M(2015)Update on epstein-barr virus and gastric cancer(review).Int J Oncol46:1421-1434
Sokolova O,Naumann M(2017)NF-kappaB signaling in gastric cancer.Toxins(Basel)9:119
Takada K,Horinouchi K,Ono Y,Aya T,Osato T,Takahashi M,Hayasaka S(1991)An epstein-barr virus-producer line akata:establishment of the cell line and analysis of viral DNA.Virus Genes 5:147-156
Tao Y,Shi Y,Jia J,Jiang Y,Yang L,Cao Y(2015)Novel roles and therapeutic targets of epstein-barr virus-encoded latent membrane protein 1-induced oncogenesis in nasopharyngeal carcinoma.Expert Rev Mol Med 17:e15
Temple RM,Zhu J,Budgeon L,Christensen ND,Meyers C,Sample CE(2014)Efficient replication of epstein-barr virus in stratified epithelium in vitro.Proc Natl Acad Sci USA 111:16544-16549
Tsao SW,Tsang CM(2017)Epstein-barr virus infection and nasopharyngeal carcinoma.Philos Trans R Soc Lond B Biol Sci 372:20160270
Tsurumi T,Fujita M,Kudoh A(2005)Latent and lytic epstein-barr virus replication strategies.Rev Med Virol 15:3-15
Tu C,Zeng Z,Qi P,Li X,Yu Z,Guo C,Xiong F,Xiang B,Zhou M,Gong Z,Liao Q,Yu J,He Y,Zhang W,Li X,Li Y,Li G,Xiong W(2017)Genome-wide analysis of 18 epstein-barr viruses isolated from primary nasopharyngeal carcinoma biopsy specimens.J Virol 91
Yao HL,Song J,Sun P,Song QQ,Sheng LJ,Chi MM,Han J(2016)Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from coxsackievirus b3-induced myocarditis.Virus Res 213:314-321
Yin Y,Si X,Gao Y,Gao L,Wang J(2013)The nuclear factor-kappab correlates with increased expression of interleukin-6 and promotes progression of gastric carcinoma.Oncol Rep 29:34-38
Young LS,Rickinson AB(2004)Epstein-barr virus:40 years on.Nat Rev Cancer 4:757-768
Yu Z,Lu J,Yu H,Yan Q,Zuo L,Li G(2011)A precise excision of the complete epstein-barr virus genome in a plasmid based on a bacterial artificial chromosome.J Virol Methods 176:103-107
Yu H,Lu J,Zuo L,Yan Q,Yu Z,Li X,Huang J,Zhao L,Tang H,Luo Z,Liao Q,Zeng Z,Zhang J,Li G(2012)Epstein-barr virus downregulates microrna 203 through the oncoprotein latent membrane protein 1:a contribution to increased tumor incidence in epithelial cells.J Virol 86:3088-3099
Zhang G,Tsang CM,Deng W,Yip YL,Lui VW,Wong SC,Cheung AL,Hau PM,Zeng M,Lung ML,Chen H,Lo KW,Takada K,Tsao SW(2013)Enhanced il-6/il-6r signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.PLoS ONE 8:e62284
Zhang H,Li Y,Wang HB,Zhang A,Chen ML,Fang ZX,Dong XD,Li SB,Du Y,Xiong D,He JY,Li MZ,Liu YM,Zhou AJ,Zhong Q,Zeng YX,Kieff E,Zhang Z,Gewurz BE,Zhao B,Zeng MS(2018)Ephrin receptor a2 is an epithelial cell receptor for epstein-barr virus entry.Nat Microbiol 3:1-8
Zhao G,Zhu G,Huang Y,Zheng W,Hua J,Yang S,Zhuang J,Ye J(2016)Il-6 mediates the signal pathway of jak-stat3-vegf-c promoting growth,invasion and lymphangiogenesis in gastric cancer.Oncol Rep 35:1787-1795
Zheng Y,Qin Z,Ye Q,Chen P,Wang Z,Yan Q,Luo Z,Liu X,Zhou Y,Xiong W,Ma J,Li G(2014)Lactoferrin suppresses the epstein-barr virus-induced inflammatory response by interfering with pattern recognition of tlr2 and tlr9.Lab Invest94:1188-1199
Zhu C,Wu Y,Chen S,Yu M,Zeng Y,You X,Xiao J,Wang S(2012)Protective immune responses in mice induced by intramuscular and intranasal immunization with a mycoplasma pneumoniae p1c DNA vaccine.Can J Microbiol 58:644-652
Zuo L,Yue W,Du S,Xin S,Zhang J,Liu L,Li G,Lu J(2017a)An update:epstein-barr virus and immune evasion via microrna regulation.Virol Sin 32:175-187
Zuo LL,Zhang J,Liu LZ,Zhou Q,Du SJ,Xin SY,Ning ZP,Yang J,Yu HB,Yue WX,Wang J,Zhu FX,Li GY,Lu JH(2017b)Cadherin 6 is activated by epstein-barr virus lmp1 to mediate emt and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.Oncogenesis 6:402
Bornkamm GW,Behrends U,Mautner J(2006)The infectious kiss:newly infected b cells deliver epstein-barr virus to epithelial cells.Proc Natl Acad Sci USA 103:7201-7202
Chakravorty M,Ghosh A,Choudhury A,Santra A,Hembrum J,Roychoudhury S(2004)Ethnic differences in allele distribution for the il8 and il1b genes in populations from eastern india.Hum Biol 76:153-159
Chen L,Yuan W,Chen Z,Wu S,Ge J,Chen J,Chen Z(2015)Vasoactive intestinal peptide represses activation of tumorassociated macrophages in gastric cancer via regulation of tnfalpha,il-6,il-12 and inos.Int J Oncol 47:1361-1370
Chen J,Sathiyamoorthy K,Zhang X,Schaller S,Perez White BE,Jardetzky TS,Longnecker R(2018)Ephrin receptor a2 is a functional entry receptor for epstein-barr virus.Nat Microbiol3:172-180
Choi SR,Lee SA,Kim YJ,Ok CY,Lee HJ,Hahm KB(2009)Role of heat shock proteins in gastric inflammation and ulcer healing.J Physiol Pharmacol 60:5-17
Chong JM,Sakuma K,Sudo M,Osawa T,Ohara E,Uozaki H,Shibahara J,Kuroiwa K,Tominaga S,Hippo Y,Aburatani H,Funata N,Fukayama M(2002)Interleukin-1beta expression in human gastric carcinoma with epstein-barr virus infection.J Virol 76:6825-6831
Cohen JI,Fauci AS,Varmus H,Nabel GJ(2011)Epstein-barr virus:an important vaccine target for cancer prevention.Sci Transl Med 3:107fs107
Dehne N,Fuhrmann D,Brune B(2013)Hypoxia-inducible factor(hif)in hormone signaling during health and disease.Cardiovasc Hematol Agents Med Chem 11:125-135
Ding L,Li L,Yang J,Zhou S,Li W,Tang M,Shi Y,Yi W,Cao Y(2007)Latent membrane protein 1 encoded by epstein-barr virus induces telomerase activity via p16ink4a/rb/e2f1 and jnk signaling pathways.J Med Virol 79:1153-1163
Ding Y,Li XR,Yang KY,Huang LH,Hu G,Gao K(2013)Proteomics analysis of gastric epithelial ags cells infected with epstein-barr virus.Asian Pac J Cancer Prev 14:367-372
Gambhir S,Vyas D,Hollis M,Aekka A,Vyas A(2015)Nuclear factor kappa b role in inflammation associated gastrointestinal malignancies.World J Gastroenterol 21:3174-3183
Henle G,Henle W,Clifford P,Diehl V,Kafuko GW,Kirya BG,Klein G,Morrow RH,Munube GM,Pike P,Tukei PM,Ziegler JL(1969)Antibodies to epstein-barr virus in burkitt’s lymphoma and control groups.J Natl Cancer Inst 43:1147-1157
Hu TZ,Huang LH,Xu CX,Liu XM,Wang Y,Xiao J,Zhou L,Luo L,Jiang XX(2015)Expressional profiles of transcription factors in the progression of helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis.Med Oncol 32:265
Hwang YS,Jeong M,Park JS,Kim MH,Lee DB,Shin BA,Mukaida N,Ellis LM,Kim HR,Ahn BW,Jung YD(2004)Interleukin-1beta stimulates il-8 expression through map kinase and ros signaling in human gastric carcinoma cells.Oncogene23:6603-6611
Lee HW,Lee EH,Kim SH,Roh MS,Jung SB,Choi YC(2013)Heat shock protein 70(hsp70)expression is associated with poor prognosis in intestinal type gastric cancer.Virchows Arch463:489-495
Li L,Zhang Y,Guo BB,Chan FK,Tao Q(2014)Oncogenic induction of cellular high cpg methylation by epstein-barr virus in malignant epithelial cells.Chin J Cancer 33:604-608
Li Y,Long X,Huang L,Yang M,Yuan Y,Wang Y,Delecluse HJ,Kuang E(2016)Epstein-barr virus bzlf1-mediated downregulation of proinflammatory factors is essential for optimal lytic viral replication.J Virol 90:887-903
Lian S,Xia Y,Ung TT,Khoi PN,Yoon HJ,Kim NH,Kim KK,Jung YD(2016)Carbon monoxide releasing molecule-2 ameliorates il-1beta-induced il-8 in human gastric cancer cells.Toxicology361-362:24-38
Liu L,Zhou Q,Xie Y,Zuo L,Zhu F,Lu J(2017)Extracellular vesicles:novel vehicles in herpesvirus infection.Virol Sin32:349-356
Lu JH,Tang YL,Yu HB,Zhou JH,Fu CY,Zeng X,Yu ZY,Yin HL,Wu MH,Zhang JY,Li XL,Li GY(2010)Epstein-barr virus facilitates the malignant potential of immortalized epithelial cells:from latent genome to viral production and maintenance.Lab Invest 90:196-209
Lu Y,Qin Z,Wang J,Zheng X,Lu J,Zhang X,Wei L,Peng Q,Zheng Y,Ou C,Ye Q,Xiong W,Li G,Fu Y,Yan Q,Ma J(2017)Epstein-barr virus mir-bart6-3p inhibits the rig-i pathway.J Innate Immun 9:574-586
Ludigs K,Parfenov V,Du Pasquier RA,Guarda G(2012)Type i ifnmediated regulation of il-1 production in inflammatory disorders.Cell Mol Life Sci 69:3395-3418
Matsusaka K,Funata S,Fukayama M,Kaneda A(2014)DNAmethylation in gastric cancer,related to helicobacter pylori and epstein-barr virus.World J Gastroenterol 20:3916-3926
McColl SR,Roberge CJ,Larochelle B,Gosselin J(1997)EBVinduces the production and release of il-8 and macrophage inflammatory protein-1 alpha in human neutrophils.J Immunol159:6164-6168
McIlwain DR,Berger T,Mak TW(2013)Caspase functions in cell death and disease.Cold Spring Harb Perspect Biol 5:a008656
Morales-Sanchez A,Fuentes-Panana EM(2014)Human viruses and cancer.Viruses 6:4047-4079
Murata T,Tsurumi T(2014)Switching of EBV cycles between latent and lytic states.Rev Med Virol 24:142-153
Nemerow GR,Mold C,Schwend VK,Tollefson V,Cooper NR(1987)Identification of gp350 as the viral glycoprotein mediating attachment of epstein-barr virus(ebv)to the ebv/c3d receptor of b cells:sequence homology of gp350 and c3complement fragment c3d.J Virol 61:1416-1420
Nemerow GR,Houghten RA,Moore MD,Cooper NR(1989)Identification of an epitope in the major envelope protein of epstein-barr virus that mediates viral binding to the b lymphocyte ebv receptor(cr2).Cell 56:369-377
Ni C,Chen Y,Zeng M,Pei R,Du Y,Tang L,Wang M,Hu Y,Zhu H,He M,Wei X,Wang S,Ning X,Wang M,Wang J,Ma L,Chen X,Sun Q,Tang H,Wang Y,Wang X(2015)In-cell infection:a novel pathway for epstein-barr virus infection mediated by cellin-cell structures.Cell Res 25:785-800
Overholtzer M,Mailleux AA,Mouneimne G,Normand G,Schnitt SJ,King RW,Cibas ES,Brugge JS(2007)A nonapoptotic cell death process,entosis,that occurs by cell-in-cell invasion.Cell131:966-979
Pereira ER,Frudd K,Awad W,Hendershot LM(2014)Endoplasmic reticulum(er)stress and hypoxia response pathways interact to potentiate hypoxia-inducible factor 1(hif-1)transcriptional activity on targets like vascular endothelial growth factor(vegf).J Biol Chem 289:3352-3364
Queiroz DM,Rocha AM,Melo FF,Rocha GA,Teixeira KN,Carvalho SD,Bittencourt PF,Castro LP,Crabtree JE(2013)Increased gastric il-1beta concentration and iron deficiency parameters in h.Pylori infected children.PLoS One 8:e57420
Savitri E,Haryana MS(2015)Expression of interleukin-8,interleukin-10 and epstein-barr viral-load as prognostic indicator in nasopharyngeal carcinoma.Glob J Health Sci 7:364-372
Shannon-Lowe CD,Neuhierl B,Baldwin G,Rickinson AB,Delecluse HJ(2006)Resting b cells as a transfer vehicle for epstein-barr virus infection of epithelial cells.Proc Natl Acad Sci USA103:7065-7070
Shinozaki-Ushiku A,Kunita A,Fukayama M(2015)Update on epstein-barr virus and gastric cancer(review).Int J Oncol46:1421-1434
Sokolova O,Naumann M(2017)NF-kappaB signaling in gastric cancer.Toxins(Basel)9:119
Takada K,Horinouchi K,Ono Y,Aya T,Osato T,Takahashi M,Hayasaka S(1991)An epstein-barr virus-producer line akata:establishment of the cell line and analysis of viral DNA.Virus Genes 5:147-156
Tao Y,Shi Y,Jia J,Jiang Y,Yang L,Cao Y(2015)Novel roles and therapeutic targets of epstein-barr virus-encoded latent membrane protein 1-induced oncogenesis in nasopharyngeal carcinoma.Expert Rev Mol Med 17:e15
Temple RM,Zhu J,Budgeon L,Christensen ND,Meyers C,Sample CE(2014)Efficient replication of epstein-barr virus in stratified epithelium in vitro.Proc Natl Acad Sci USA 111:16544-16549
Tsao SW,Tsang CM(2017)Epstein-barr virus infection and nasopharyngeal carcinoma.Philos Trans R Soc Lond B Biol Sci 372:20160270
Tsurumi T,Fujita M,Kudoh A(2005)Latent and lytic epstein-barr virus replication strategies.Rev Med Virol 15:3-15
Tu C,Zeng Z,Qi P,Li X,Yu Z,Guo C,Xiong F,Xiang B,Zhou M,Gong Z,Liao Q,Yu J,He Y,Zhang W,Li X,Li Y,Li G,Xiong W(2017)Genome-wide analysis of 18 epstein-barr viruses isolated from primary nasopharyngeal carcinoma biopsy specimens.J Virol 91
Yao HL,Song J,Sun P,Song QQ,Sheng LJ,Chi MM,Han J(2016)Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from coxsackievirus b3-induced myocarditis.Virus Res 213:314-321
Yin Y,Si X,Gao Y,Gao L,Wang J(2013)The nuclear factor-kappab correlates with increased expression of interleukin-6 and promotes progression of gastric carcinoma.Oncol Rep 29:34-38
Young LS,Rickinson AB(2004)Epstein-barr virus:40 years on.Nat Rev Cancer 4:757-768
Yu Z,Lu J,Yu H,Yan Q,Zuo L,Li G(2011)A precise excision of the complete epstein-barr virus genome in a plasmid based on a bacterial artificial chromosome.J Virol Methods 176:103-107
Yu H,Lu J,Zuo L,Yan Q,Yu Z,Li X,Huang J,Zhao L,Tang H,Luo Z,Liao Q,Zeng Z,Zhang J,Li G(2012)Epstein-barr virus downregulates microrna 203 through the oncoprotein latent membrane protein 1:a contribution to increased tumor incidence in epithelial cells.J Virol 86:3088-3099
Zhang G,Tsang CM,Deng W,Yip YL,Lui VW,Wong SC,Cheung AL,Hau PM,Zeng M,Lung ML,Chen H,Lo KW,Takada K,Tsao SW(2013)Enhanced il-6/il-6r signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.PLoS ONE 8:e62284
Zhang H,Li Y,Wang HB,Zhang A,Chen ML,Fang ZX,Dong XD,Li SB,Du Y,Xiong D,He JY,Li MZ,Liu YM,Zhou AJ,Zhong Q,Zeng YX,Kieff E,Zhang Z,Gewurz BE,Zhao B,Zeng MS(2018)Ephrin receptor a2 is an epithelial cell receptor for epstein-barr virus entry.Nat Microbiol 3:1-8
Zhao G,Zhu G,Huang Y,Zheng W,Hua J,Yang S,Zhuang J,Ye J(2016)Il-6 mediates the signal pathway of jak-stat3-vegf-c promoting growth,invasion and lymphangiogenesis in gastric cancer.Oncol Rep 35:1787-1795
Zheng Y,Qin Z,Ye Q,Chen P,Wang Z,Yan Q,Luo Z,Liu X,Zhou Y,Xiong W,Ma J,Li G(2014)Lactoferrin suppresses the epstein-barr virus-induced inflammatory response by interfering with pattern recognition of tlr2 and tlr9.Lab Invest94:1188-1199
Zhu C,Wu Y,Chen S,Yu M,Zeng Y,You X,Xiao J,Wang S(2012)Protective immune responses in mice induced by intramuscular and intranasal immunization with a mycoplasma pneumoniae p1c DNA vaccine.Can J Microbiol 58:644-652
Zuo L,Yue W,Du S,Xin S,Zhang J,Liu L,Li G,Lu J(2017a)An update:epstein-barr virus and immune evasion via microrna regulation.Virol Sin 32:175-187
Zuo LL,Zhang J,Liu LZ,Zhou Q,Du SJ,Xin SY,Ning ZP,Yang J,Yu HB,Yue WX,Wang J,Zhu FX,Li GY,Lu JH(2017b)Cadherin 6 is activated by epstein-barr virus lmp1 to mediate emt and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.Oncogenesis 6:402