1887

Abstract

Reactivation of latent human cytomegalovirus is a significant infectious complication of organ transplantation and current therapies target viral replication once reactivation of latent virus has already occurred. The specific molecular pathways that activate viral gene expression in response to transplantation are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. Murine cytomegalovirus (MCMV) is a valuable model for studying latency and reactivation of CMV . We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces reactivation of immediate early (IE) gene expression and epigenetic reprogramming of the major immediate early promoter (MIEP) within 48 h. We hypothesize that these events are mediated by activation of signalling pathways that lead to binding of transcription factors to the MIEP, including AP-1 and NF-κB. Here we show that transplantation induces rapid activation of several members of the AP-1 and NF-κB transcription factor family and we demonstrate that canonical NF-κB (p65/p50), the junD component of AP-1, and nucleosome remodelling complexes are recruited to the MIEP following transplantation. Proteomic analysis of recipient plasma and transcriptome analysis of kidney RNA identified five extracellular ligands, including TNF, IL-1β, IL-18, CD40L and IL-6, and three intracellular signalling pathways associated with reactivation of IE gene expression. Identification of the factors that mediate activation of these signalling pathways may eventually lead to new therapies to prevent reactivation of CMV and its sequelae.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000407
2016-04-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/4/941.html?itemId=/content/journal/jgv/10.1099/jgv.0.000407&mimeType=html&fmt=ahah

References

  1. Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. 1990; A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J 9:1897–1906[PubMed]
    [Google Scholar]
  2. Angulo A., Ghazal P., Messerle M. 2000; The major immediate-early gene ie3 of mouse cytomegalovirus is essential for viral growth. J Virol 74:11129–11136 [View Article][PubMed]
    [Google Scholar]
  3. Baccam M., Woo S. Y., Vinson C., Bishop G. A. 2003; CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: involvement of NF-kappa B, AP-1, and C/EBP. J Immunol 170:3099–3108 [View Article][PubMed]
    [Google Scholar]
  4. Beutler B. A., Milsark I. W., Cerami A. 1985; Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 135:3972–3977[PubMed]
    [Google Scholar]
  5. Bode J. G., Ludwig S., Freitas C. A., Schaper F., Ruhl M., Melmed S., Heinrich P. C., Häussinger D. 2001; The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription. Biol Chem 382:1447–1453 [View Article][PubMed]
    [Google Scholar]
  6. Bolstad B. M., Irizarry R. A., Astrand M., Speed T. P. 2003; A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193 [View Article][PubMed]
    [Google Scholar]
  7. Chen C. Y., Shyu A. B. 1995; AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 20:465–470 [View Article][PubMed]
    [Google Scholar]
  8. Cook C. H., Yenchar J. K., Kraner T. O., Davies E. A., Ferguson R. M. 1998; Occult herpes family viruses may increase mortality in critically ill surgical patients. Am J Surg 176:357–360 [View Article][PubMed]
    [Google Scholar]
  9. Cook C. H., Trgovcich J., Zimmerman P. D., Zhang Y., Sedmak D. D. 2006; Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1beta triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol 80:9151–9158 [View Article][PubMed]
    [Google Scholar]
  10. de Groot H., Rauen U. 2007; Ischemia-reperfusion injury: processes in pathogenetic networks: a review. Transplant Proc 39:481–484 [View Article][PubMed]
    [Google Scholar]
  11. Döcke W. D., Fietze E., Syrbe U., von Baehr R., Volk H. D., Prösch S., Kimel V., Krüger D. H., Zuckermann H., Klug C. 1994; Cytomegalovirus reactivation and tumour necrosis factor. Lancet 343:268–269 [View Article][PubMed]
    [Google Scholar]
  12. Dorsch-Häsler K., Keil G. M., Weber F., Jasin M., Schaffner W., Koszinowski U. H. 1985; A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proc Natl Acad Sci U S A 82:8325–8329 [View Article][PubMed]
    [Google Scholar]
  13. Eferl R., Wagner E. F. 2003; AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3:859–868 [View Article][PubMed]
    [Google Scholar]
  14. Einecke G., Melk A., Ramassar V., Zhu L. F., Bleackley R. C., Famulski K. S., Halloran P. F. 2005; Expression of CTL associated transcripts precedes the development of tubulitis in T-cell mediated kidney graft rejection. Am J Transplant 5:1827–1836 [View Article][PubMed]
    [Google Scholar]
  15. Eisenhart C. 1947; The assumptions underlying the analysis of variance. Biometrics 3:1–21 [View Article][PubMed]
    [Google Scholar]
  16. El-Sawy T., Miura M., Fairchild R. 2004; Early T cell response to allografts occurring prior to alloantigen priming up-regulates innate-mediated inflammation and graft necrosis. Am J Pathol 165:147–157 [View Article][PubMed]
    [Google Scholar]
  17. Famulski K. S., Einecke G., Reeve J., Ramassar V., Allanach K., Mueller T., Hidalgo L. G., Zhu L. F., Halloran P. F. 2006; Changes in the transcriptome in allograft rejection: IFN-gamma-induced transcripts in mouse kidney allografts. Am J Transplant 6:1342–1354 [View Article][PubMed]
    [Google Scholar]
  18. Famulski K. S., Broderick G., Einecke G., Hay K., Cruz J., Sis B., Mengel M., Halloran P. F. 2007; Transcriptome analysis reveals heterogeneity in the injury response of kidney transplants. Am J Transplant 7:2483–2495 [View Article][PubMed]
    [Google Scholar]
  19. Fietze E., Prösch S., Reinke P., Stein J., Döcke W. D., Staffa G., Löning S., Devaux S., Emmrich F., other authors. 1994; Cytomegalovirus infection in transplant recipients. The role of tumor necrosis factor. Transplantation 58:675–680 [View Article][PubMed]
    [Google Scholar]
  20. Fishman J. A., Emery V., Freeman R., Pascual M., Rostaing L., Schlitt H. J., Sgarabotto D., Torre-Cisneros J., Uknis M. E. 2007; Cytomegalovirus in transplantation – challenging the status quo. Clin Transplant 21:149–158 [View Article][PubMed]
    [Google Scholar]
  21. Gallucci S., Lolkema M., Matzinger P. 1999; Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5:1249–1255 [View Article][PubMed]
    [Google Scholar]
  22. Gerald D., Berra E., Frapart Y. M., Chan D. A., Giaccia A. J., Mansuy D., Pouysségur J., Yaniv M., Mechta-Grigoriou F. 2004; JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118:781–794 [View Article][PubMed]
    [Google Scholar]
  23. Gloire G., Legrand-Poels S., Piette J. 2006; NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 72:1493–1505 [View Article][PubMed]
    [Google Scholar]
  24. Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. 1989; Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA 261:3561–3566 [View Article][PubMed]
    [Google Scholar]
  25. Grzimek N. K., Dreis D., Schmalz S., Reddehase M. J. 2001; Random, asynchronous, and asymmetric transcriptional activity of enhancer-flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalovirus latency in the lungs. J Virol 75:2692–2705 [View Article][PubMed]
    [Google Scholar]
  26. Gupta S., Barrett T., Whitmarsh A. J., Cavanagh J., Sluss H. K., Dérijard B., Davis R. J. 1996; Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15:2760–2770[PubMed]
    [Google Scholar]
  27. Hargett D., Shenk T. E. 2010; Experimental human cytomegalovirus latency in CD14+ monocytes. Proc Natl Acad Sci U S A 107:20039–20044 [View Article][PubMed]
    [Google Scholar]
  28. Hargreaves D. C., Horng T., Medzhitov R. 2009; Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138:129–145 [View Article][PubMed]
    [Google Scholar]
  29. Heininger A., Jahn G., Engel C., Notheisen T., Unertl K., Hamprecht K. 2001; Human cytomegalovirus infections in nonimmunosuppressed critically ill patients [see comments]. Crit Care Med 29:541–547 [View Article][PubMed]
    [Google Scholar]
  30. Heinrich P. C., Behrmann I., Haan S., Hermanns H. M., Müller-Newen G., Schaper F. 2003; Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20 [View Article][PubMed]
    [Google Scholar]
  31. Hernandez J. M., Floyd D. H., Weilbaecher K. N., Green P. L., Boris-Lawrie K. 2008; Multiple facets of junD gene expression are atypical among AP-1 family members. Oncogene 27:4757–4767 [View Article][PubMed]
    [Google Scholar]
  32. Hibberd P. L., Tolkoff-Rubin N. E., Cosimi A. B., Schooley R. T., Isaacson D., Doran M., Delvecchio A., Delmonico F. L., Auchincloss H., Jr., Rubin R. H. 1992; Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipient treated with OKT3. Transplantation 53:68–72 [View Article][PubMed]
    [Google Scholar]
  33. Huang M. M., Kew V. G., Jestice K., Wills M. R., Reeves M. B. 2012; Efficient human cytomegalovirus reactivation is maturation dependent in the Langerhans dendritic cell lineage and can be studied using a CD14+ experimental latency model. J Virol 86:8507–8515 [View Article][PubMed]
    [Google Scholar]
  34. Hummel M., Abecassis M. M. 2002; A model for reactivation of CMV from latency. J Clin Virol 25:(Suppl 2)123–136 [View Article][PubMed]
    [Google Scholar]
  35. Hummel M., Zhang Z., Yan S., DePlaen I., Golia P., Varghese T., Thomas G., Abecassis M. I. 2001; Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency. J Virol 75:4814–4822 [View Article][PubMed]
    [Google Scholar]
  36. Hummel M., Kurian S. M., Lin S., Borodyanskiy A., Zhang Z., Li Z., Kim S. J., Salomon D. R., Abecassis M. 2009; Intragraft TNF receptor signaling contributes to activation of innate and adaptive immunity in a renal allograft model. Transplantation 87:178–188 [View Article][PubMed]
    [Google Scholar]
  37. Jaeschke A., Karasarides M., Ventura J. J., Ehrhardt A., Zhang C., Flavell R. A., Shokat K. M., Davis R. J. 2006; JNK2 is a positive regulator of the cJun transcription factor. Mol Cell 23:899–911 [View Article][PubMed]
    [Google Scholar]
  38. Kadam S., Emerson B. M. 2003; Transcriptional specificity of human SWI/SNF BRG1 and BRM chromatin remodeling complexes. Mol Cell 11:377–389 [View Article][PubMed]
    [Google Scholar]
  39. Kalil A. C., Florescu D. F. 2009; Prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit. Crit Care Med 37:2350–2358 [View Article][PubMed]
    [Google Scholar]
  40. Kamata H., Honda S., Maeda S., Chang L., Hirata H., Karin M. 2005; Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661 [View Article][PubMed]
    [Google Scholar]
  41. Karin M. 1995; The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270:16483–16486 [View Article][PubMed]
    [Google Scholar]
  42. Karin M., Shaulian E. 2001; AP-1: linking hydrogen peroxide and oxidative stress to the control of cell proliferation and death. IUBMB Life 52:17–24 [View Article][PubMed]
    [Google Scholar]
  43. Keil G. M., Ebeling-Keil A., Koszinowski U. H. 1987a; Immediate-early genes of murine cytomegalovirus: location, transcripts, and translation products. J Virol 61:526–533[PubMed]
    [Google Scholar]
  44. Keil G. M., Ebeling-Keil A., Koszinowski U. H. 1987b; Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. J Virol 61:1901–1908[PubMed]
    [Google Scholar]
  45. Kew V. G., Yuan J., Meier J., Reeves M. B. 2014; Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency. PLoS Pathog 10:e1004195 [View Article][PubMed]
    [Google Scholar]
  46. Kim S. J., Varghese T. K., Zhang Z., Zhao L. C., Thomas G., Hummel M., Abecassis M. 2005; Renal ischemia/reperfusion injury activates the enhancer domain of the human cytomegalovirus major immediate early promoter. Am J Transplant 5:1606–1613 [View Article][PubMed]
    [Google Scholar]
  47. Kono H., Rock K. L. 2008; How dying cells alert the immune system to danger. Nat Rev Immunol 8:279–289 [View Article][PubMed]
    [Google Scholar]
  48. Kropp K. A., Angulo A., Ghazal P. 2014; Viral enhancer mimicry of host innate-immune promoters. PLoS Pathog 10:e1003804 [View Article][PubMed]
    [Google Scholar]
  49. Kurz S., Steffens H. P., Mayer A., Harris J. R., Reddehase M. J. 1997; Latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs. J Virol 71:2980–2987[PubMed]
    [Google Scholar]
  50. Kurz S. K., Rapp M., Steffens H. P., Grzimek N. K., Schmalz S., Reddehase M. J. 1999; Focal transcriptional activity of murine cytomegalovirus during latency in the lungs. J Virol 73:482–494[PubMed]
    [Google Scholar]
  51. Kutza A. S., Muhl E., Hackstein H., Kirchner H., Bein G. 1998; High incidence of active cytomegalovirus infection among septic patients [see comments]. Clin Infect Dis 26:1076–1082 [View Article][PubMed]
    [Google Scholar]
  52. Lamb J. A., Ventura J. J., Hess P., Flavell R. A., Davis R. J. 2003; JunD mediates survival signaling by the JNK signal transduction pathway. Mol Cell 11:1479–1489 [View Article][PubMed]
    [Google Scholar]
  53. Lao W. C., Lee D., Burroughs A. K., Lanzani G., Rolles K., Emery V. C., Griffiths P. D. 1997; Use of polymerase chain reaction to provide prognostic information on human cytomegalovirus disease after liver transplantation. J Med Virol 51:152–158 [View Article][PubMed]
    [Google Scholar]
  54. Lee Y., Sohn W. J., Kim D. S., Kwon H. J. 2004; NF-kappaB- and c-Jun-dependent regulation of human cytomegalovirus immediate-early gene enhancer/promoter in response to lipopolysaccharide and bacterial CpG-oligodeoxynucleotides in macrophage cell line RAW 264.7. Eur J Biochem 271:1094–1105 [View Article][PubMed]
    [Google Scholar]
  55. Li Z., Wang X., Yan S., Zhang Z., Jie C., Sustento-Reodica N., Hummel M., Abecassis M. 2012; A mouse model of CMV transmission following kidney transplantation. Am J Transplant 12:1024–1028 [View Article][PubMed]
    [Google Scholar]
  56. Limaye A. P., Kirby K. A., Rubenfeld G. D., Leisenring W. M., Bulger E. M., Neff M. J., Gibran N. S., Huang M. L., Santo Hayes T. K., other authors. 2008; Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 300:413–422 [View Article][PubMed]
    [Google Scholar]
  57. Liu X. F., Yan S., Abecassis M., Hummel M. 2008; Establishment of murine cytomegalovirus latency in vivo is associated with changes in histone modifications and recruitment of transcriptional repressors to the major immediate-early promoter. J Virol 82:10922–10931 [View Article][PubMed]
    [Google Scholar]
  58. Liu X. F., Yan S., Abecassis M., Hummel M. 2010; Biphasic recruitment of transcriptional repressors to the murine cytomegalovirus major immediate-early promoter during the course of infection in vivo. J Virol 84:3631–3643 [View Article][PubMed]
    [Google Scholar]
  59. Liu X. F., Wang X., Yan S., Zhang Z., Abecassis M., Hummel M. 2013; Epigenetic control of cytomegalovirus latency and reactivation. Viruses 5:1325–1345 [View Article][PubMed]
    [Google Scholar]
  60. Mann J., Oakley F., Johnson P. W., Mann D. A. 2002; CD40 induces interleukin-6 gene transcription in dendritic cells: regulation by TRAF2, AP-1, NF-kappa B, and CBF1. J Biol Chem 277:17125–17138 [View Article][PubMed]
    [Google Scholar]
  61. Martínez F. P., Cosme R. S., Tang Q. 2010; Murine cytomegalovirus major immediate-early protein 3 interacts with cellular and viral proteins in viral DNA replication compartments and is important for early gene activation. J Gen Virol 91:2664–2676 [View Article][PubMed]
    [Google Scholar]
  62. Medzhitov R., Horng T. 2009; Transcriptional control of the inflammatory response. Nat Rev Immunol 9:692–703 [View Article][PubMed]
    [Google Scholar]
  63. Meier J. L., Stinski M. F. 2013; Major immediate-early enhancer and its gene products. In Cytomegaloviruses: From Molecular Pathogenesis to Intervention pp 152–173Edited by Reddehase M. J. Norfolk, UK: Caister Academic Press;
    [Google Scholar]
  64. Messerle M., Bühler B., Keil G. M., Koszinowski U. H. 1992; Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3. J Virol 66:27–36[PubMed]
    [Google Scholar]
  65. Mocarski E. S., Shenk T., Pass R. F. 2007; Cytomegaloviruses. In Fields Virology, 5th edn. pp 2702–2772Edited by Knipe D. M., Howley P. M. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins;
    [Google Scholar]
  66. Mohrmann L., Verrijzer C. P. 2005; Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes. Biochim Biophys Acta 1681:59–73 [View Article][PubMed]
    [Google Scholar]
  67. Morgan M. J., Liu Z. G. 2011; Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 21:103–115 [View Article][PubMed]
    [Google Scholar]
  68. Mutimer D., Mirza D., Shaw J., O'Donnell K., Elias E. 1997; Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients. Transplantation 63:1411–1415 [View Article][PubMed]
    [Google Scholar]
  69. Ndlovu M. N., Van Lint C., Van Wesemael K., Callebert P., Chalbos D., Haegeman G., Vanden Berghe W. 2009; Hyperactivated NF-kappaB and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells. Mol Cell Biol 29:5488–5504 [View Article][PubMed]
    [Google Scholar]
  70. O'Connor C. M., Murphy E. A. 2012; A myeloid progenitor cell line capable of supporting human cytomegalovirus latency and reactivation, resulting in infectious progeny. J Virol 86:9854–9865 [View Article][PubMed]
    [Google Scholar]
  71. Oeckinghaus A., Hayden M. S., Ghosh S. 2011; Crosstalk in NF-κB signaling pathways. Nat Immunol 12:695–708 [View Article][PubMed]
    [Google Scholar]
  72. Pillebout E., Weitzman J. B., Burtin M., Martino C., Federici P., Yaniv M., Friedlander G., Terzi F. 2003; JunD protects against chronic kidney disease by regulating paracrine mitogens. J Clin Invest 112:843–852 [View Article][PubMed]
    [Google Scholar]
  73. Pomerantz J. L., Baltimore D. 2002; Two pathways to NF-kappaB. Mol Cell 10:693–695 [View Article][PubMed]
    [Google Scholar]
  74. Portela D., Patel R., Larson-Keller J. J., Ilstrup D. M., Wiesner R. H., Steers J. L., Krom R. A., Paya C. V. 1995; OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation. J Infect Dis 171:1014–1018 [View Article][PubMed]
    [Google Scholar]
  75. Prösch S., Staak K., Stein J., Liebenthal C., Stamminger T., Volk H.-D., Krüger D. H. 1995; Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB. Virology 208:197–206 [View Article][PubMed]
    [Google Scholar]
  76. Quezada S. A., Jarvinen L. Z., Lind E. F., Noelle R. J. 2004; CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307–328 [View Article][PubMed]
    [Google Scholar]
  77. Ramirez-Carrozzi V. R., Nazarian A. A., Li C. C., Gore S. L., Sridharan R., Imbalzano A. N., Smale S. T. 2006; Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20:282–296 [View Article][PubMed]
    [Google Scholar]
  78. Ramirez-Carrozzi V. R., Braas D., Bhatt D. M., Cheng C. S., Hong C., Doty K. R., Black J. C., Hoffmann A., Carey M., Smale S. T. 2009; A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 138:114–128 [View Article][PubMed]
    [Google Scholar]
  79. Razonable R. R., Rivero A., Rodriguez A., Wilson J., Daniels J., Jenkins G., Larson T., Hellinger W. C., Spivey J. R., Paya C. V. 2001; Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis 184:1461–1464 [View Article][PubMed]
    [Google Scholar]
  80. Razonable R. R., Humar A., AST Infectious Diseases Community of Practice. 2013; Cytomegalovirus in solid organ transplantation. Am J Transplant 13:(Suppl 4)93–106 [View Article][PubMed]
    [Google Scholar]
  81. Reeves M. B., Compton T. 2011; Inhibition of inflammatory interleukin-6 activity via extracellular signal-regulated kinase-mitogen-activated protein kinase signaling antagonizes human cytomegalovirus reactivation from dendritic cells. J Virol 85:12750–12758 [View Article][PubMed]
    [Google Scholar]
  82. Reeves M., Sinclair J. 2013; Epigenetic regulation of human cytomegalovirus gene expression: impact on latency and reactivation. In Cytomegaloviruses: From Molecular Pathogenesis to Intervention pp 330–346Edited by Reddehase M. J. Norfolk, UK: Caister Academic Press;
    [Google Scholar]
  83. Reeves M. B., MacAry P. A., Lehner P. J., Sissons J. G., Sinclair J. H. 2005; Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad Sci U S A 102:4140–4145 [View Article][PubMed]
    [Google Scholar]
  84. Reinke P., Fietze E., Döcke W. D., Kern F., Ewert R., Volk H. D. 1994a; Late acute rejection in long-term renal allograft recipients. Diagnostic and predictive value of circulating activated T cells. Transplantation 58:35–41 [View Article][PubMed]
    [Google Scholar]
  85. Reinke P., Fietze E., Ode-Hakim S., Prösch S., Lippert J., Ewert R., Volk H. D. 1994b; Late-acute renal allograft rejection and symptomless cytomegalovirus infection. Lancet 344:1737–1738 [View Article][PubMed]
    [Google Scholar]
  86. Ruland J. 2011; Return to homeostasis: downregulation of NF-κB responses. Nat Immunol 12:709–714 [View Article][PubMed]
    [Google Scholar]
  87. Sasaki T., Kojima H., Kishimoto R., Ikeda A., Kunimoto H., Nakajima K. 2006; Spatiotemporal regulation of c-Fos by ERK5 and the E3 ubiquitin ligase UBR1, and its biological role. Mol Cell 24:63–75 [View Article][PubMed]
    [Google Scholar]
  88. Seckert C. K., Griebl M., Buttner J., Freitag K., Lemmermann N., Hummel M., Liu X.-F., Abecassis M., Angulo A., other authors. 2013; Immune surveillance of cytomegalovirus latency and reactivation in murine models: link to ‘memory inflation’. In Cytomegaloviruses: From Molecular Pathogenesis to Therapy pp 374–416Edited by Reddehase M. J. Norfolk, UK: Caister Academic Press;
    [Google Scholar]
  89. Shaulian E., Karin M. 2002; AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136 [View Article][PubMed]
    [Google Scholar]
  90. Simon C. O., Seckert C. K., Dreis D., Reddehase M. J., Grzimek N. K. 2005; Role for tumor necrosis factor alpha in murine cytomegalovirus transcriptional reactivation in latently infected lungs. J Virol 79:326–340 [View Article][PubMed]
    [Google Scholar]
  91. Smart D. E., Vincent K. J., Arthur M. J., Eickelberg O., Castellazzi M., Mann J., Mann D. A. 2001; JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and interleukin-6 genes in activated hepatic stellate cells. J Biol Chem 276:24414–24421 [View Article][PubMed]
    [Google Scholar]
  92. Söderberg-Nauclér C., Fish K. N., Nelson J. A. 1997; Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 91:119–126 [View Article][PubMed]
    [Google Scholar]
  93. Stein J., Volk H. D., Liebenthal C., Krüger D. H., Prösch S. 1993; Tumour necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J Gen Virol 74:2333–2338 [View Article][PubMed]
    [Google Scholar]
  94. Stenberg R. M., Thomsen D. R., Stinski M. F. 1991; Structural analysis of the major immediate early gene of human cytomegalovirus. J Virol 49:190–984[PubMed]
    [Google Scholar]
  95. Teferedegne B., Green M. R., Guo Z., Boss J. M. 2006; Mechanism of action of a distal NF-kappaB-dependent enhancer. Mol Cell Biol 26:5759–5770 [View Article][PubMed]
    [Google Scholar]
  96. Tsuji Y. 2005; JunD activates transcription of the human ferritin H gene through an antioxidant response element during oxidative stress. Oncogene 24:7567–7578 [View Article][PubMed]
    [Google Scholar]
  97. Viedt C., Dechend R., Fei J., Hänsch G. M., Kreuzer J., Orth S. R. 2002; MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1. J Am Soc Nephrol 13:1534–1547 [View Article][PubMed]
    [Google Scholar]
  98. Weber A., Wasiliew P., Kracht M. 2010; Interleukin-1 (IL-1) pathway. Sci Signal 3:cm1[PubMed]
    [Google Scholar]
  99. Wolter S., Doerrie A., Weber A., Schneider H., Hoffmann E., von der Ohe J., Bakiri L., Wagner E. F., Resch K., Kracht M. 2008; c-Jun controls histone modifications, NF-kappaB recruitment, and RNA polymerase II function to activate the ccl2 gene. Mol Cell Biol 28:4407–4423 [View Article][PubMed]
    [Google Scholar]
  100. Wullaert A., Heyninck K., Beyaert R. 2006; Mechanisms of crosstalk between TNF-induced NF-kappaB and JNK activation in hepatocytes. Biochem Pharmacol 72:1090–1101 [View Article][PubMed]
    [Google Scholar]
  101. Zerbini L. F., Wang Y., Cho J. Y., Libermann T. A. 2003; Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer. Cancer Res 63:2206–2215[PubMed]
    [Google Scholar]
  102. Zhang Z., Schlachta C., Duff J., Stiller C., Grant D., Zhong R. 1995; Improved techniques for kidney transplantation in mice. Microsurgery 16:103–109 [View Article][PubMed]
    [Google Scholar]
  103. Zhang Z., Kim S. J., Varghese T., Thomas G., Hummel M., Abecassis M. 2008; TNF receptor independent activation of the cytomegalovirus major immediate early enhancer in response to transplantation. Transplantation 85:1039–1045 [View Article][PubMed]
    [Google Scholar]
  104. Zhang Z., Li Z., Yan S., Wang X., Abecassis M. 2009; TNF-alpha signaling is not required for in vivo transcriptional reactivation of latent murine cytomegalovirus. Transplantation 88:640–645 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000407
Loading
/content/journal/jgv/10.1099/jgv.0.000407
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error