1887

Abstract

Graft rejection in transplant patients is managed clinically by suppressing T-cell function with immunosuppressive drugs such as prednisolone and methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) is an important opportunistic pathogen and can cause severe morbidity and mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV in the presence of GCSs. In the present study, we explored the implications of steroid exposure on latency and reactivation. We observed a direct effect of several GCSs used in the clinic on the activation of a quiescent viral major immediate-early promoter in stably transfected THP-1 monocytic cells. This activation was prevented by the glucocorticoid receptor (GR) antagonist Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this observation, prednisolone treatment of latently infected primary monocytes resulted in HCMV reactivation. Analysis of the phenotype of these cells showed that treatment with GCSs was correlated with differentiation to an anti-inflammatory macrophage-like cell type. On the basis that these observations may be pertinent to HCMV reactivation in post-transplant settings, we retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in liver transplant patients in the presence or absence of GCS treatment. We observed that combination therapy of baseline prednisolone and augmented methylprednisolone, upon organ rejection, significantly increased the incidence of HCMV infection in the intermediate risk group where donor and recipient are both HCMV seropositive (D+R+) to levels comparable with the high risk D+R− group.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.069872-0
2015-01-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/1/131.html?itemId=/content/journal/jgv/10.1099/vir.0.069872-0&mimeType=html&fmt=ahah

References

  1. Alexopoulou L., Holt A. C., Medzhitov R., Flavell R. A. 2001; Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738 [View Article][PubMed]
    [Google Scholar]
  2. Almawi W. Y., Melemedjian O. K., Rieder M. J. 1999; An alternate mechanism of glucocorticoid anti-proliferative effect: promotion of a Th2 cytokine-secreting profile. Clin Transplant 13:365–374 [View Article][PubMed]
    [Google Scholar]
  3. Archin N. M., Liberty A. L., Kashuba A. D., Choudhary S. K., Kuruc J. D., Crooks A. M., Parker D. C., Anderson E. M., Kearney M. F.other authors 2012; Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487:482–485 [View Article][PubMed]
    [Google Scholar]
  4. Arrode G., Davrinche C. 2003; Dendritic cells and HCMV cross-presentation. Curr Top Microbiol Immunol 276:277–294[PubMed]
    [Google Scholar]
  5. Atabani S. F., Smith C., Atkinson C., Aldridge R. W., Rodriguez-Perálvarez M., Rolando N., Harber M., Jones G., O’Riordan A.other authors 2012; Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy. Am J Transplant 12:2457–2464 [View Article][PubMed]
    [Google Scholar]
  6. Bayer C., Varani S., Wang L., Walther P., Zhou S., Straschewski S., Bachem M., Söderberg-Naucler C., Mertens T., Frascaroli G. 2013; Human cytomegalovirus infection of M1 and M2 macrophages triggers inflammation and autologous T-cell proliferation. J Virol 87:67–79 [View Article][PubMed]
    [Google Scholar]
  7. Bego M., Maciejewski J., Khaiboullina S., Pari G., St Jeor S. 2005; Characterization of an antisense transcript spanning the UL81-82 locus of human cytomegalovirus. J Virol 79:11022–11034 [View Article][PubMed]
    [Google Scholar]
  8. Bego M. G., Keyes L. R., Maciejewski J., St Jeor S. C. 2011; Human cytomegalovirus latency-associated protein LUNA is expressed during HCMV infections in vivo. Arch Virol 156:1847–1851 [View Article][PubMed]
    [Google Scholar]
  9. Boeckh M., Nichols W. G. 2004; The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 103:2003–2008 [View Article][PubMed]
    [Google Scholar]
  10. Bolovan-Fritts C. A., Mocarski E. S., Wiedeman J. A. 1999; Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood 93:394–398[PubMed]
    [Google Scholar]
  11. Bristow B. N., O’Keefe K. A., Shafir S. C., Sorvillo F. J. 2011; Congenital cytomegalovirus mortality in the United States, 1990-2006. PLoS Negl Trop Dis 5:e1140 [View Article][PubMed]
    [Google Scholar]
  12. Buckingham J. C. 2006; Glucocorticoids: exemplars of multi-tasking. Br J Pharmacol 147:Suppl 1S258–S268 [View Article][PubMed]
    [Google Scholar]
  13. Bunde T., Kirchner A., Hoffmeister B., Habedank D., Hetzer R., Cherepnev G., Proesch S., Reinke P., Volk H. D.other authors 2005; Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J Exp Med 201:1031–1036 [View Article][PubMed]
    [Google Scholar]
  14. Cadepond F., Ulmann A., Baulieu E. E. 1997; RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med 48:129–156 [View Article][PubMed]
    [Google Scholar]
  15. Cherrington J. M., Mocarski E. S. 1989; Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element. J Virol 63:1435–1440[PubMed]
    [Google Scholar]
  16. Cherrington J. M., Khoury E. L., Mocarski E. S. 1991; Human cytomegalovirus ie2 negatively regulates alpha gene expression via a short target sequence near the transcription start site. J Virol 65:887–896[PubMed]
    [Google Scholar]
  17. Cope A. V., Sabin C., Burroughs A., Rolles K., Griffiths P. D., Emery V. C. 1997; Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J Infect Dis 176:1484–1490 [View Article][PubMed]
    [Google Scholar]
  18. Crough T., Khanna R. 2009; Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev 22:76–98 [View Article][PubMed]
    [Google Scholar]
  19. Cwynarski K., Ainsworth J., Cobbold M., Wagner S., Mahendra P., Apperley J., Goldman J., Craddock C., Moss P. A. 2001; Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation. Blood 97:1232–1240 [View Article][PubMed]
    [Google Scholar]
  20. DuRose J. B., Li J., Chien S., Spector D. H. 2012; Infection of vascular endothelial cells with human cytomegalovirus under fluid shear stress reveals preferential entry and spread of virus in flow conditions simulating atheroprone regions of the artery. J Virol 86:13745–13755 [View Article][PubMed]
    [Google Scholar]
  21. Ehrchen J., Steinmüller L., Barczyk K., Tenbrock K., Nacken W., Eisenacher M., Nordhues U., Sorg C., Sunderkötter C., Roth J. 2007; Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes. Blood 109:1265–1274 [View Article][PubMed]
    [Google Scholar]
  22. Gamadia L. E., Remmerswaal E. B., Weel J. F., Bemelman F., van Lier R. A., Ten Berge I. J. 2003; Primary immune responses to human CMV: a critical role for IFN-gamma-producing CD4+ T cells in protection against HCMV disease. Blood 101:2686–2692 [View Article][PubMed]
    [Google Scholar]
  23. Ghazal P., Lubon H., Reynolds-Kohler C., Hennighausen L., Nelson J. A. 1990; Interactions between cellular regulatory proteins and a unique sequence region in the human cytomegalovirus major immediate-early promoter. Virology 174:18–25 [View Article][PubMed]
    [Google Scholar]
  24. Goodrum F. D., Jordan C. T., High K., Shenk T. 2002; Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency. Proc Natl Acad Sci U S A 99:16255–16260 [View Article][PubMed]
    [Google Scholar]
  25. Goodrum F., Reeves M., Sinclair J., High K., Shenk T. 2007; Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro. Blood 110:937–945 [View Article][PubMed]
    [Google Scholar]
  26. Gratama J. W., van Esser J. W., Lamers C. H., Tournay C., Löwenberg B., Bolhuis R. L., Cornelissen J. J. 2001; Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive HCMV infection. Blood 98:1358–1364 [View Article][PubMed]
    [Google Scholar]
  27. Griffiths P. D., Stanton A., McCarrell E., Smith C., Osman M., Harber M., Davenport A., Jones G., Wheeler D. C.other authors 2011; Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial. Lancet 377:1256–1263 [View Article][PubMed]
    [Google Scholar]
  28. Groves I. J., Reeves M. B., Sinclair J. H. 2009; Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic ‘pre-immediate-early’ repression of viral gene expression mediated by histone post-translational modification. J Gen Virol 90:2364–2374 [View Article][PubMed]
    [Google Scholar]
  29. Hahn G., Jores R., Mocarski E. S. 1998; Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci U S A 95:3937–3942 [View Article][PubMed]
    [Google Scholar]
  30. 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]
  31. Hebart H., Daginik S., Stevanovic S., Grigoleit U., Dobler A., Baur M., Rauser G., Sinzger C., Jahn G.other authors 2002; Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T-lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation. Blood 99:3830–3837 [View Article][PubMed]
    [Google Scholar]
  32. Huang T. H., Oka T., Asai T., Okada T., Merrills B. W., Gertson P. N., Whitson R. H., Itakura K. 1996; Repression by a differentiation-specific factor of the human cytomegalovirus enhancer. Nucleic Acids Res 24:1695–1701 [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. Humar A., Snydman D.AST Infectious Diseases Community of Practice 2009; Cytomegalovirus in solid organ transplant recipients. Am J Transplant 9:Suppl. 4S78–S86 [View Article][PubMed]
    [Google Scholar]
  35. Husain S., Pietrangeli C. E., Zeevi A. 2009; Delayed onset HCMV disease in solid organ transplant recipients. Transpl Immunol 21:1–9 [View Article][PubMed]
    [Google Scholar]
  36. Ioudinkova E., Arcangeletti M. C., Rynditch A., De Conto F., Motta F., Covan S., Pinardi F., Razin S. V., Chezzi C. 2006; Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line. Gene 384:120–128 [View Article][PubMed]
    [Google Scholar]
  37. Jenkins C., Abendroth A., Slobedman B. 2004; A novel viral transcript with homology to human interleukin-10 is expressed during latent human cytomegalovirus infection. J Virol 78:1440–1447 [View Article][PubMed]
    [Google Scholar]
  38. Jenkins C., Garcia W., Godwin M. J., Spencer J. V., Stern J. L., Abendroth A., Slobedman B. 2008; Immunomodulatory properties of a viral homolog of human interleukin-10 expressed by human cytomegalovirus during the latent phase of infection. J Virol 82:3736–3750 [View Article][PubMed]
    [Google Scholar]
  39. Joyce D. A., Steer J. H., Abraham L. J. 1997; Glucocorticoid modulation of human monocyte/macrophage function: control of TNF-alpha secretion. Inflamm Res 46:447–451 [View Article][PubMed]
    [Google Scholar]
  40. Keyes L. R., Bego M. G., Soland M., St Jeor S. 2012; Cyclophilin A is required for efficient human cytomegalovirus DNA replication and reactivation. J Gen Virol 93:722–732 [View Article][PubMed]
    [Google Scholar]
  41. Kotton C. N., Kumar D., Caliendo A. M., Asberg A., Chou S., Danziger-Isakov L., Humar A.Transplantation Society International HCMV Consensus Group 2013; Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 96:333–360 [View Article][PubMed]
    [Google Scholar]
  42. Krause H., Hebart H., Jahn G., Müller C. A., Einsele H. 1997; Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset HCMV disease. Bone Marrow Transplant 19:1111–1116 [View Article][PubMed]
    [Google Scholar]
  43. Kumar A., Zhang J., Yu F. S. 2006; Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells. Immunology 117:11–21 [View Article][PubMed]
    [Google Scholar]
  44. Kurz S. K., Reddehase M. J. 1999; Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73:8612–8622[PubMed]
    [Google Scholar]
  45. 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]
  46. Lang D., Stamminger T. 1993; The 86-kilodalton IE-2 protein of human cytomegalovirus is a sequence-specific DNA-binding protein that interacts directly with the negative autoregulatory response element located near the cap site of the IE-1/2 enhancer-promoter. J Virol 67:323–331[PubMed]
    [Google Scholar]
  47. Lathey J. L., Spector S. A. 1991; Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. J Virol 65:6371–6375[PubMed]
    [Google Scholar]
  48. Limaye A. P., Bakthavatsalam R., Kim H. W., Randolph S. E., Halldorson J. B., Healey P. J., Kuhr C. S., Levy A. E., Perkins J. D.other authors 2006; Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis. Transplantation 81:1645–1652 [View Article][PubMed]
    [Google Scholar]
  49. Littell R. C., Milliken G. A., Stroup W. W., Wolfinger R. D., Schabenberger O. 2006 SAS for Mixed Models, 2nd edn. Cary, NC: SAS Institute;
    [Google Scholar]
  50. Ljungman P., Hakki M., Boeckh M. 2011; Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am 25:151–169 [View Article][PubMed]
    [Google Scholar]
  51. Lubon H., Ghazal P., Hennighausen L., Reynolds-Kohler C., Lockshin C., Nelson J. 1989; Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene. Mol Cell Biol 9:1342–1345[PubMed]
    [Google Scholar]
  52. Macias M. P., Stinski M. F. 1993; An in vitro system for human cytomegalovirus immediate early 2 protein (IE2)-mediated site-dependent repression of transcription and direct binding of IE2 to the major immediate early promoter. Proc Natl Acad Sci U S A 90:707–711 [View Article][PubMed]
    [Google Scholar]
  53. Mendelson M., Monard S., Sissons P., Sinclair J. 1996; Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 77:3099–3102 [View Article][PubMed]
    [Google Scholar]
  54. Montag C., Wagner J. A., Gruska I., Vetter B., Wiebusch L., Hagemeier C. 2011; The latency-associated UL138 gene product of human cytomegalovirus sensitizes cells to tumor necrosis factor alpha (TNF-alpha) signaling by upregulating TNF-alpha receptor 1 cell surface expression. J Virol 85:11409–11421 [View Article][PubMed]
    [Google Scholar]
  55. Nebbia G., Mattes F. M., Sabin C. A., Samonakis D., Rolando N., Burroughs A. K., Emery V. C. 2007; Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation. Transplantation 84:605–610 [View Article][PubMed]
    [Google Scholar]
  56. O’Connor C. M., Shenk T. 2012; Human cytomegalovirus pUL78 G protein-coupled receptor homologue is required for timely cell entry in epithelial cells but not fibroblasts. J Virol 86:11425–11433 [View Article][PubMed]
    [Google Scholar]
  57. Ozdemir E., St John L. S., Gillespie G., Rowland-Jones S., Champlin R. E., Molldrem J. J., Komanduri K. V. 2002; Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells. Blood 100:3690–3697 [View Article][PubMed]
    [Google Scholar]
  58. Paliogianni F., Ahuja S. S., Balow J. P., Balow J. E., Boumpas D. T. 1993; Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor. J Immunol 151:4081–4089[PubMed]
    [Google Scholar]
  59. Parker L. C., Whyte M. K., Vogel S. N., Dower S. K., Sabroe I. 2004; Toll-like receptor (TLR)2 and TLR4 agonists regulate CCR expression in human monocytic cells. J Immunol 172:4977–4986 [View Article][PubMed]
    [Google Scholar]
  60. Pevsner-Fischer M., Morad V., Cohen-Sfady M., Rousso-Noori L., Zanin-Zhorov A., Cohen S., Cohen I. R., Zipori D. 2007; Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 109:1422–1432 [View Article][PubMed]
    [Google Scholar]
  61. Phillips R. J., Lutz M., Premack B. 2005; Differential signaling mechanisms regulate expression of CC chemokine receptor-2 during monocyte maturation. J Inflamm (Lond) 2:14 [View Article][PubMed]
    [Google Scholar]
  62. Pratt W. B., Morishima Y., Murphy M., Harrell M. 2006; Chaperoning of glucocorticoid receptors. Handbook Exp Pharmacol 172:111–138 [View Article][PubMed]
    [Google Scholar]
  63. Reeves M. B. 2011; Chromatin-mediated regulation of cytomegalovirus gene expression. Virus Res 157:134–143 [View Article][PubMed]
    [Google Scholar]
  64. Reeves M., Sissons P., Sinclair J. 2005a; Reactivation of human cytomegalovirus in dendritic cells. Discov Med 5:170–174[PubMed]
    [Google Scholar]
  65. Reeves M. B., Lehner P. J., Sissons J. G., Sinclair J. H. 2005b; An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J Gen Virol 86:2949–2954 [View Article][PubMed]
    [Google Scholar]
  66. Reeves M. B., MacAry P. A., Lehner P. J., Sissons J. G., Sinclair J. H. 2005c; 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]
  67. Reusser P., Riddell S. R., Meyers J. D., Greenberg P. D. 1991; Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 78:1373–1380[PubMed]
    [Google Scholar]
  68. Reusser P., Cathomas G., Attenhofer R., Tamm M., Thiel G. 1999; Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from HCMV disease by limiting the systemic virus load. J Infect Dis 180:247–253 [View Article][PubMed]
    [Google Scholar]
  69. Scott G. M., Ratnamohan V. M., Rawlinson W. D. 2000; Improving permissive infection of human cytomegalovirus in cell culture. Arch Virol 145:2431–2438 [View Article][PubMed]
    [Google Scholar]
  70. Sinclair J. 2010; Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection. Biochim Biophys Acta 1799:286–295 [View Article][PubMed]
    [Google Scholar]
  71. Sindre H., Tjøonnfjord G. E., Rollag H., Ranneberg-Nilsen T., Veiby O. P., Beck S., Degré M., Hestdal K. 1996; Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood 88:4526–4533[PubMed]
    [Google Scholar]
  72. Sinzger C., Bissinger A. L., Viebahn R., Oettle H., Radke C., Schmidt C. A., Jahn G. 1999a; Hepatocytes are permissive for human cytomegalovirus infection in human liver cell culture and in vivo. J Infect Dis 180:976–986 [View Article][PubMed]
    [Google Scholar]
  73. Sinzger C., Schmidt K., Knapp J., Kahl M., Beck R., Waldman J., Hebart H., Einsele H., Jahn G. 1999b; Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome. J Gen Virol 80:2867–2877[PubMed]
    [Google Scholar]
  74. Sissons J. G., Bain M., Wills M. R. 2002; Latency and reactivation of human cytomegalovirus. J Infect 44:73–77 [View Article][PubMed]
    [Google Scholar]
  75. Söderberg-Nauclér C., Fish K. N., Nelson J. A. 1997; Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines. J Clin Invest 100:3154–3163 [View Article][PubMed]
    [Google Scholar]
  76. Söderberg-Nauclér C., Streblow D. N., Fish K. N., Allan-Yorke J., Smith P. P., Nelson J. A. 2001; Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J Virol 75:7543–7554 [View Article][PubMed]
    [Google Scholar]
  77. Springer K. L., Weinberg A. 2004; Cytomegalovirus infection in the era of HAART: fewer reactivations and more immunity. J Antimicrob Chemother 54:582–586 [View Article][PubMed]
    [Google Scholar]
  78. St George K., Rinaldo C. R. Jr 1994; Effects of enhancing agents on detection of cytomegalovirus in clinical specimens. J Clin Microbiol 32:2024–2027[PubMed]
    [Google Scholar]
  79. Stenberg R. M., Witte P. R., Stinski M. F. 1985; Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1. J Virol 56:665–675[PubMed]
    [Google Scholar]
  80. Stinski M. F., Thomsen D. R., Stenberg R. M., Goldstein L. C. 1983; Organization and expression of the immediate early genes of human cytomegalovirus. J Virol 46:1–14[PubMed]
    [Google Scholar]
  81. Straschewski S., Warmer M., Frascaroli G., Hohenberg H., Mertens T., Winkler M. 2010; Human cytomegaloviruses expressing yellow fluorescent fusion proteins–characterization and use in antiviral screening. PLoS ONE 5:e9174 [View Article][PubMed]
    [Google Scholar]
  82. Tanaka J., Ogura T., Kamiya S., Sato H., Yoshie T., Ogura H., Hatano M. 1984; Enhanced replication of human cytomegalovirus in human fibroblasts treated with dexamethasone. J Gen Virol 65:1759–1767 [View Article][PubMed]
    [Google Scholar]
  83. Taylor-Wiedeman J., Sissons P., Sinclair J. 1994; Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol 68:1597–1604[PubMed]
    [Google Scholar]
  84. van der Velden V. H. 1998; Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma. Mediators Inflamm 7:229–237 [View Article][PubMed]
    [Google Scholar]
  85. Verreck F. A., de Boer T., Langenberg D. M., van der Zanden L., Ottenhoff T. H. 2006; Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-γ- and CD40L-mediated costimulation. J Leukoc Biol 79:285–293 [View Article][PubMed]
    [Google Scholar]
  86. Volpin R., Angeli P., Galioto A., Fasolato S., Neri D., Barbazza F., Merenda R., Del Piccolo F., Strazzabosco M.other authors 2002; Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial. Liver Transpl 8:527–534 [View Article][PubMed]
    [Google Scholar]
  87. Wathen M. W., Stinski M. F. 1982; Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol 41:462–477[PubMed]
    [Google Scholar]
  88. Weinshenker B. G., Wilton S., Rice G. P. 1988; Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol 140:1625–1631[PubMed]
    [Google Scholar]
  89. West P. G., Aldrich B., Hartwig R., Haller G. J. 1988; Enhanced detection of cytomegalovirus in confluent MRC-5 cells treated with dexamethasone and dimethyl sulfoxide. J Clin Microbiol 26:2510–2514[PubMed]
    [Google Scholar]
  90. Zhang J. H., Chung T. D., Oldenburg K. R. 1999; A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen 4:67–73 [View Article][PubMed]
    [Google Scholar]
  91. Zhuravskaya T., Maciejewski J. P., Netski D. M., Bruening E., Mackintosh F. R., St Jeor S. 1997; Spread of human cytomegalovirus (HCMV) after infection of human hematopoietic progenitor cells: model of HCMV latency. Blood 90:2482–2491[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.069872-0
Loading
/content/journal/jgv/10.1099/vir.0.069872-0
Loading

Data & Media loading...

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