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Cytomegalovirus Cell Tropism

  • C. Sinzger
  • M. Digel
  • G. Jahn
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 325)

The human cytomegalovirus (HCMV) can infect a remarkably broad cell range within its host, including parenchymal cells and connective tissue cells of virtually any organ and various hematopoietic cell types. Epithelial cells, endothelial cells, fibroblasts and smooth muscle cells are the predominant targets for virus replication. The pathogenesis of acute HCMV infections is greatly influenced by this broad target cell range. Infection of epithelial cells presumably contributes to interhost transmission. Infection of endothelial cells and hematopoietic cells facilitates systemic spread within the host. Infection of ubiquitous cell types such as fibroblasts and smooth muscle cells provides the platform for efficient proliferation of the virus.

The tropism for endothelial cells, macrophages and dendritic cells varies greatly among different HCMV strains, mostly dependent on alterations within the UL128- 131 gene locus. In line with the classification of the respective proteins as structural components of the viral envelope, interstrain differences concerning the infectivity in endothelial cells and macrophages are regulated on the level of viral entry.

Keywords

Human Cytomegalovirus Cytomegalovirus Infection HCMV Infection Cardiac Allograft Vasculopathy Cell Tropism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U (2006) Role of human cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol 87:2451–2460PubMedCrossRefGoogle Scholar
  2. Albrecht T, Weller TH (1980) Heterogeneous morphologic features of plaques induced by five strains of human cytomegalovirus. Am J Clin Pathol 73:648–654PubMedGoogle Scholar
  3. Balazs M (1984) Electron microscopic examination of congenital cytomegalovirus hepatitis. Virchows Arch A Pathol Anat Histopathol 405:119–129PubMedCrossRefGoogle Scholar
  4. Baldanti F, Paolucci S, Campanini G, Sarasini A, Percivalle E, Revello MG, Gerna G (2006) Human cytomegalovirus UL131A, UL130 and UL128 genes are highly conserved among field isolates. Arch Virol 151:1225–1233PubMedCrossRefGoogle Scholar
  5. Bissinger AL, Sinzger C, Kaiserling E, Jahn G (2002) Human cytomegalovirus as a direct pathogen: correlation of multiorgan involvement and cell distribution with clinical and pathological findings in a case of congenital inclusion disease. J Med Virol 67:200–206PubMedCrossRefGoogle Scholar
  6. Bissinger AL, Oettle H, Jahn G, Neuhaus P, Sinzger C (2004) Cytomegalovirus infection after orthotopic liver transplantation is restricted by a pre-existing antiviral immune response of the recipient. J Med Virol 73:45–53PubMedCrossRefGoogle Scholar
  7. Bodaghi B, Slobbe-van Drunen ME, Topilko A, Perret E, Vossen RC, van Dam-Mieras MC, Zipeto D, Virelizier JL, LeHoang P, Bruggeman CA, Michelson S (1999) Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest Ophthalmol Vis Sci 40:2598–2607PubMedGoogle Scholar
  8. Brune W, Menard C, Heesemann J, Koszinowski UH (2001) A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science 291:303–305PubMedCrossRefGoogle Scholar
  9. Digel M, Sinzger C (2006) Determinants of endothelial cell tropism of human cytomegalovirus. In: Reddehase MJ (ed) Cytomegaloviruses: molecular biology and immunology. Caister Academic Press, Norfolk, pp 445–464Google Scholar
  10. Donnellan WL, Chantra-Umporn S, Kidd JM (1966) The cytomegalic inclusion cell. An electron microscopic study. Arch Pathol 82:336–348PubMedGoogle Scholar
  11. Dunn W, Chou C, Li H, Hai R, Patterson D, Stolc V, Zhu H, Liu F (2003) Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci USA 100:14223–14228PubMedCrossRefGoogle Scholar
  12. Emery VC, Cope AV, Bowen EF, Gor D, Griffiths PD (1999) The dynamics of human cytomegalovirus replication in vivo. J Exp Med 190:177–182PubMedCrossRefGoogle Scholar
  13. Francis ND, Boylston AW, Roberts AH, Parkin JM, Pinching AJ (1989) Cytomegalovirus infection in gastrointestinal tracts of patients infected with HIV-1 or AIDS. J Clin Pathol 42:1055–1064PubMedCrossRefGoogle Scholar
  14. Gerna G, Zipeto D, Parea M, Revello MG, Silini E, Percivalle E, Zavattoni M, Grossi P, Milanesi G (1991) Monitoring of human cytomegalovirus infections and ganciclovir treatment in heart transplant recipients by determination of viremia, antigenemia, and DNAemia. J Infect Dis 164:488–498PubMedGoogle Scholar
  15. Gerna G, Zipeto D, Percivalle E, Parea M, Revello MG, Maccario R, Peri G, Milanesi G (1992) Human cytomegalovirus infection of the major leukocyte subpopulations and evidence for initial viral replication in polymorphonuclear leukocytes from viremic patients. J Infect Dis 166:1236–1244PubMedGoogle Scholar
  16. Genta RM, Bleyzer I, Cate TR, Tandon AK, Yoffe B (1993) In situ hybridization and immunohistochemical analysis of cytomegalovirus-associated ileal perforation. Gastroenterology 104:1822–1827PubMedGoogle Scholar
  17. Gerna G, Percivalle E, Baldanti F, Sozzani S, Lanzarini P, Genini E, Lilleri D, Revello MG (2000) Human cytomegalovirus replicates abortively in polymorphonuclear leukocytes after transfer from infected endothelial cells via transient microfusion events. J Virol 74:5629–5638PubMedCrossRefGoogle Scholar
  18. Gilbert GL, Hayes K, Hudson IL, James J (1989) Prevention of transfusion-acquired cytomegalovirus infection in infants by blood filtration to remove leucocytes. Neonatal Cytomegalovirus Infection Study Group. Lancet 1:1228–1231PubMedCrossRefGoogle Scholar
  19. Grefte A, Blom N, van der Giessen M, van Son W, The TH (1993) Ultrastructural analysis of circulating cytomegalic cells in patients with active cytomegalovirus infection: evidence for virus production and endothelial origin. J Infect Dis 168:1110–1118PubMedGoogle Scholar
  20. Grefte A, Harmsen MC, van der Giessen M, Knollema S, van Son WJ, The TH (1994) Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection. J Gen Virol 75:1989–1998PubMedCrossRefGoogle Scholar
  21. Grigoleit U, Riegler S, Einsele H, Laib Sampaio K, Jahn G, Hebart H, Brossart P, Frank F, Sinzger C (2002) Human cytomegalovirus induces a direct inhibitory effect on antigen presentation by monocyte-derived immature dendritic cells. Br J Haematol 119:189–198PubMedCrossRefGoogle Scholar
  22. Hahn G, Khan H, Baldanti F, Koszinowski UH, Revello MG, Gerna G (2002) The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable for growth in endothelial cells, as determined by a BAC-cloned clinical isolate of human cytomegalovirus with preserved wild-type characteristics. J Virol 76:9551–9555PubMedCrossRefGoogle Scholar
  23. Hahn G, Revello MG, Patrone M, Percivalle E, Campanini G, Sarasini A, Wagner M, Gallina A, Milanesi G, Koszinowski U, Baldanti F, Gerna G (2004) Human cytomegalovirus UL131–128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78:10023–10033PubMedCrossRefGoogle Scholar
  24. Halwachs-Baumann G, Wilders-Truschnig M, Desoye G, Hahn T, Kiesel L, Klingel K, Rieger P, Jahn G, Sinzger C (1998) Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus. J Virol 72:7598–7602PubMedGoogle Scholar
  25. Hamprecht K, Maschmann J, Vochem M, Dietz K, Speer CP, Jahn G (2001) Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Lancet 357:513–518PubMedCrossRefGoogle Scholar
  26. Hamprecht K, Maschmann J, Vochem M, Speer CP, Jahn G (2003) Transmission of cytomegalovirus to preterm infants by breast-feeding. In: Proesch S, Cinatl J, Scholz M (eds) New aspects of CMV-related immunopathology, vol 24. Karger, Basel, pp 33–42CrossRefGoogle Scholar
  27. Hanson LK, Slater JS, Karabekian Z, Ciocco-Schmitt G, Campbell AE (2001) Products of US22 genes M140 and M141 confer efficient replication of murine cytomegalovirus in macrophages and spleen. J Virol 75:6292–6302PubMedCrossRefGoogle Scholar
  28. Heieren MH, Kim YK, Balfour HH Jr (1988) Human cytomegalovirus infection of kidney glomerular visceral epithelial and tubular epithelial cells in culture. Transplantation 46:426–432PubMedCrossRefGoogle Scholar
  29. Hertel L, Lacaille VG, Strobl H, Mellins ED, Mocarski ES (2003) Susceptibility of immature and mature Langerhans cell-type dendritic cells to infection and immunomodulation by human cytomegalovirus. J Virol 77:7563–7574PubMedCrossRefGoogle Scholar
  30. Ho DD, Rota TR, Andrews CA, Hirsch MS (1984) Replication of human cytomegalovirus in endothelial cells. J Infect Dis 150:956–957PubMedGoogle Scholar
  31. Ibanez CE, Schrier R, Ghazal P, Wiley C, Nelson JA (1991) Human cytomegalovirus productively infects primary differentiated macrophages. J Virol 65:6581–6588PubMedGoogle Scholar
  32. Jahn G, Stenglein S, Riegler S, Einsele H, Sinzger C (1999) Human cytomegalovirus infection of immature dendritic cells and macrophages. Intervirology 42:365–372PubMedCrossRefGoogle Scholar
  33. Jonjic S, Mutter W, Weiland F, Reddehase MJ, Koszinowski UH (1989) Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. J Exp Med 169:1199–1212PubMedCrossRefGoogle Scholar
  34. Kahl M, Siegel-Axel D, Stenglein S, Jahn G, Sinzger C (2000) Efficient lytic infection of human arterial endothelial cells by human cytomegalovirus strains. J Virol 74:7628–7635PubMedCrossRefGoogle Scholar
  35. Kasnic G Jr, Sayeed A, Azar HA (1982) Nuclear and cytoplasmic inclusions in disseminated human cytomegalovirus infection. Ultrastruct Pathol 3:229–235PubMedCrossRefGoogle Scholar
  36. Kinzler ER, Compton T (2005) Characterization of human cytomegalovirus glycoprotein-induced cell-cell fusion. J Virol 79:7827–7837PubMedCrossRefGoogle Scholar
  37. Kloover JS, Hillebrands JL, de Wit G, Grauls G, Rozing J, Bruggeman CA, Nieuwenhuis P (2000) Rat cytomegalovirus replication in the salivary glands is exclusively confined to striated duct cells. Virchows Arch 437:413–421PubMedCrossRefGoogle Scholar
  38. Lathey JL, Spector SA (1991) Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. J Virol 65:6371–6375PubMedGoogle Scholar
  39. Martin AM Jr, Kurtz SM (1966) Cytomegalic inclusion disease. An electron microscopic histochemical study of the virus at necropsy. Arch Pathol 82:27–34PubMedGoogle Scholar
  40. Menard C, Wagner M, Ruzsics Z, Holak K, Brune W, Campbell AE, Koszinowski UH (2003) Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J Virol 77:5557–5570PubMedCrossRefGoogle Scholar
  41. Mocarski ES, Shenk T, Pass RF (2006) Cytomegaloviruses. In: Knipe DM (ed) Fields virology. Lippincott Williams and Wilkins, Philadelphia, pp 2701–2772Google Scholar
  42. Moutaftsi M, Mehl AM, Borysiewicz LK, Tabi Z (2002) Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells. Blood 99:2913–2921PubMedCrossRefGoogle Scholar
  43. Myerson D, Hackman RC, Nelson JA, Ward DC, McDougall JK (1984) Widespread presence of histologically occult cytomegalovirus. Hum Pathol 15:430–439PubMedCrossRefGoogle Scholar
  44. Ng Bautista CL, Sedmak DD (1995) Cytomegalovirus infection is associated with absence of alveolar epithelial cell HLA class II antigen expression. J Infect Dis 171:39–44PubMedGoogle Scholar
  45. Patrone M, Percivalle E, Secchi M, Fiorina L, Pedrali-Noy G, Zoppe M, Baldanti F, Hahn G, Koszinowski UH, Milanesi G, Gallina A (2003) The human cytomegalovirus UL45 gene product is a late, virion-associated protein and influences virus growth at low multiplicities of infection. J Gen Virol 84:3359–3370PubMedCrossRefGoogle Scholar
  46. Patrone M, Secchi M, Fiorina L, Ierardi M, Milanesi G, Gallina A (2005) Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J Virol 79:8361–8373PubMedCrossRefGoogle Scholar
  47. Plachter B, Sinzger C, Jahn G (1996) Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 46:195–261PubMedCrossRefGoogle Scholar
  48. Podlech J, Holtappels R, Wirtz N, Steffens HP, Reddehase MJ (1998) Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation. J Gen Virol 79:2099–2104PubMedGoogle Scholar
  49. Podlech J, Holtappels R, Pahl-Seibert MF, Steffens HP, Reddehase MJ (2000) Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection. J Virol 74:7496–7507PubMedCrossRefGoogle Scholar
  50. Poland SD, Costello P, Dekaban GA, Rice GP (1990) Cytomegalovirus in the brain: in vitro infection of human brain-derived cells. J Infect Dis 162:1252–1262PubMedGoogle Scholar
  51. Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA (2006) Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation 82:398–405PubMedCrossRefGoogle Scholar
  52. Raftery MJ, Schwab M, Eibert SM, Samstag Y, Walczak H, Schonrich G (2001) Targeting the function of mature dendritic cells by human cytomegalovirus: a multilayered viral defense strategy. Immunity 15:997–1009PubMedCrossRefGoogle Scholar
  53. Reddehase MJ, Weiland F, Munch K, Jonjic S, Luske A, Koszinowski UH (1985) Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol 55:264–273PubMedGoogle Scholar
  54. Reeves MB, Lehner PJ, Sissons JG, Sinclair JH (2005) An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J Gen Virol 86:2949–2954PubMedCrossRefGoogle Scholar
  55. Reinhardt B, Vaida B, Voisard R, Keller L, Breul J, Metzger H, Herter T, Baur R, Luske A, Mertens T (2003) Human cytomegalovirus infection in human renal arteries in vitro. J Virol Methods 109:1–9PubMedCrossRefGoogle Scholar
  56. Reinhardt B, Winkler M, Schaarschmidt P, Pretsch R, Zhou S, Vaida B, Schmid-Kotsas A, Michel D, Walther P, Bachem M, Mertens T (2006) Human cytomegalovirus-induced reduction of extracellular matrix proteins in vascular smooth muscle cell cultures: a pathomechanism in vasculopathies? J Gen Virol 87:2849–2858PubMedCrossRefGoogle Scholar
  57. Rice GP, Schrier RD, Oldstone MB (1984) Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci USA 81:6134–6138PubMedCrossRefGoogle Scholar
  58. Riegler S, Hebart H, Einsele H, Brossart P, Jahn G, Sinzger C (2000) Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus. J Gen Virol 81:393–399PubMedGoogle Scholar
  59. Roberts WH, Sneddon JM, Waldman J, Stephens RE (1989) Cytomegalovirus infection of gastrointestinal endothelium demonstrated by simultaneous nucleic acid hybridization and immunohistochemistry. Arch Pathol Lab Med 113:461–464PubMedGoogle Scholar
  60. Rummelt V, Rummelt C, Jahn G, Wenkel H, Sinzger C, Mayer UM, Naumann GO (1994) Triple retinal infection with human immunodeficiency virus type 1, cytomegalovirus, and herpes simplex virus type 1. Light and electron microscopy, immunohistochemistry, and in situ hybridization. Ophthalmology 101:270–279PubMedGoogle Scholar
  61. Schafer P, Tenschert W, Cremaschi L, Schroter M, Gutensohn K, Laufs R (2000) Cytomegalovirus cultured from different major leukocyte subpopulations: association with clinical features in CMV immunoglobulin G-positive renal allograft recipients. J Med Virol 61:488–496PubMedCrossRefGoogle Scholar
  62. Schmidbauer M, Budka H, Ulrich W, Ambros P (1989) Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry and in situ DNA hybridization. Acta Neuropathol (Berl) 79:286–293CrossRefGoogle Scholar
  63. Schwartz DA, Walker B, Furlong B, Breding E, Someren A (1990) Cytomegalovirus in a macerated second trimester fetus: persistent viral inclusions on light and electron microscopy. South Med J 83:1357–1358PubMedGoogle Scholar
  64. Shelbourn SL, Sissons JG, Sinclair JH (1989) Expression of oncogenic ras in human teratocarcinoma cells induces partial differentiation and permissiveness for human cytomegalovirus infection. J Gen Virol 70:367–374PubMedCrossRefGoogle Scholar
  65. Sinclair J, Sissons P (2006) Latency and reactivation of human cytomegalovirus. J Gen Virol 87:1763–1779PubMedCrossRefGoogle Scholar
  66. Sinzger C (2008) Entry route of HCMV into endothelial cells. J Clin Virol 41:174–179PubMedCrossRefGoogle Scholar
  67. Sinzger C, Muntefering H, Loning T, Stoss H, Plachter B, Jahn G (1993) Cell types infected in human cytomegalovirus placentitis identified by immunohistochemical double staining. Virchows Arch A Pathol Anat Histopathol 423:249–256PubMedCrossRefGoogle Scholar
  68. Sinzger C, Plachter B, Grefte A, The TH, Jahn G (1996) Tissue macrophages are infected by human cytomegalovirus in vivo. J Infect Dis 173:240–245PubMedGoogle Scholar
  69. Sinzger C, Grefte A, Plachter B, Gouw AS, The TH, Jahn G (1995) Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 76:741–750PubMedCrossRefGoogle Scholar
  70. Sinzger C, Jahn G (1996) Human cytomegalovirus cell tropism and pathogenesis. Intervirology 39:302–319PubMedGoogle Scholar
  71. Sinzger C, Bissinger AL, Viebahn R, Oettle H, Radke C, Schmidt CA, Jahn G (1999a) Hepatocytes are permissive for human cytomegalovirus infection in human liver cell culture and In vivo. J Infect Dis 180:976–986PubMedCrossRefGoogle Scholar
  72. 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 80:2867–2877PubMedGoogle Scholar
  73. Sinzger C, Kahl M, Laib K, Klingel K, Rieger P, Plachter B, Jahn G (2000) Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus. J Gen Virol 81:3021–3035PubMedGoogle Scholar
  74. Sinzger C, Eberhardt K, Cavignac Y, Weinstock C, Kessler T, Jahn G, Davignon JL (2006) Macrophage cultures are susceptible to lytic productive infection by endothelial-cell-propagated human cytomegalovirus strains and present viral IE1 protein to CD4+ T cells despite late downregulation of MHC class II molecules. J Gen Virol 87:1853–1862PubMedCrossRefGoogle Scholar
  75. Skaletskaya A, Bartle LM, Chittenden T, McCormick AL, Mocarski ES, Goldmacher VS (2001) A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc Natl Acad Sci USA 98:7829–7834PubMedCrossRefGoogle Scholar
  76. Spiller OB, Borysiewicz LK, Morgan BP (1997) Development of a model for cytomegalovirus infection of oligodendrocytes. J Gen Virol 78:3349–3356PubMedGoogle Scholar
  77. Stagno S, Cloud GA (1994) Working parents: the impact of day care and breast-feeding on cytomegalovirus infections in offspring. Proc Natl Acad Sci USA 91:2384–2389PubMedCrossRefGoogle Scholar
  78. Stassen FR, Vega-Cordova X, Vliegen I, Bruggeman CA (2006) Immune activation following cytomegalovirus infection: more important than direct viral effects in cardiovascular disease? J Clin Virol 35:349–353PubMedCrossRefGoogle Scholar
  79. Streblow DN, van Cleef KW, Kreklywich CN, Meyer C, Smith P, Defilippis V, Grey F, Fruh K, Searles R, Bruggeman C, Vink C, Nelson JA, Orloff SL (2007) Rat cytomegalovirus gene expression in cardiac allograft recipients is tissue specific and does not parallel the profiles detected in vitro. J Virol 81:3816–3826PubMedCrossRefGoogle Scholar
  80. Tabi Z, Moutaftsi M, Borysiewicz LK (2001) Human cytomegalovirus pp65- and immediate early 1 antigen-specific HLA class I-restricted cytotoxic T cell responses induced by cross-presentation of viral antigens. J Immunol 166:5695–5703PubMedGoogle Scholar
  81. The TH, van der Bij W, van den Berg AP, van der Giessen M, Weits J, Sprenger HG, van Son WJ (1990) Cytomegalovirus antigenemia. Rev Infect Dis 12 Suppl 7: S734–S744PubMedGoogle Scholar
  82. Tugizov S, Maidji E, Pereira L (1996) Role of apical and basolateral membranes in replication of human cytomegalovirus in polarized retinal pigment epithelial cells. J Gen Virol 77:61–74PubMedCrossRefGoogle Scholar
  83. Tumilowicz JJ, Gawlik ME, Powell BB, Trentin JJ (1985) Replication of cytomegalovirus in human arterial smooth muscle cells. J Virol 56:839–845PubMedGoogle Scholar
  84. Valantine HA (2004) The role of viruses in cardiac allograft vasculopathy. Am J Transplant 4:169–177PubMedCrossRefGoogle Scholar
  85. van Den Pol AN, Mocarski E, Saederup N, Vieira J, Meier TJ (1999) Cytomegalovirus cell tropism, replication, and gene transfer in brain. J Neurosci 19:10948–10965Google Scholar
  86. van der Strate BW, Hillebrands JL, Lycklama a Nijeholt SS, Beljaars L, Bruggeman CA, Van Luyn MJ, Rozing J, The TH, Meijer DK, Molema G, Harmsen MC (2003) Dissemination of rat cytomegalovirus through infected granulocytes and monocytes in vitro and in vivo. J Virol 77:11274–11278PubMedCrossRefGoogle Scholar
  87. Variend S, Pearse RG (1986) Sudden infant death and cytomegalovirus inclusion disease. J Clin Pathol 39:383–386PubMedCrossRefGoogle Scholar
  88. Waldman WJ, Sneddon JM, Stephens RE, Roberts WH (1989) Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells. J Med Virol 28:223–230PubMedCrossRefGoogle Scholar
  89. Waldman WJ, Roberts WH, Davis DH, Williams MV, Sedmak DD, Stephens RE (1991) Preservation of natural endothelial cytopathogenicity of cytomegalovirus by propagation in endothelial cells. Arch Virol 117:143–164PubMedCrossRefGoogle Scholar
  90. Waldman WJ, Knight DA, Huang EH, Sedmak DD (1995) Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model. J Infect Dis 171:263–272PubMedGoogle Scholar
  91. Wang D, Shenk T (2005a) Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J Virol 79:10330–10338PubMedCrossRefGoogle Scholar
  92. Wang D, Shenk T (2005b) Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci USA 102:18153–18158PubMedCrossRefGoogle Scholar
  93. Wiley CA, Nelson JA (1988) Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am J Pathol 133:73–81PubMedGoogle Scholar
  94. Yamane Y, Furukawa T, Plotkin SA (1983) Supernatant virus release as a differentiating marker between low passage and vaccine strains of human cytomegalovirus. Vaccine 1:23–25PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • C. Sinzger
    • 1
  • M. Digel
    • 1
  • G. Jahn
    • 1
  1. 1.Institute of Medical VirologyUniversity of TübingenGermany

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