Endothelial cells in human cytomegalovirus infection: One host cell out of many or a crucial target for virus spread?

 

 Buy Article Permissions and Reprints

Summary

Endothelial cells (EC) are assumed to play a central role in the spread of human cytomegalovirus (HCMV) throughout the body. Results from in-situ analyses of infected tissues and data from cell culture systems together strongly suggest that vascular EC can support productive replication of HCMV and thus contribute to its haematogeneous dissemination. By inducing an angiogenic response, HCMV may even promote growth of its own habitat. The particular role of EC is further supported by the fact that entry of HCMV into EC is dependent on a complex of the envelope glycoproteins gH and gL with a set of proteins (UL128–131A) which is dispensable for HCMV entry into most other cell types. These molecular requirements may also be reflected by cell type-dependent differences in entry routes, i.e. endocytosis versus fusion at the plasma membrane. An animal model with trackable murine CMV is now available to clarify the pathogenetic role of EC during haematogeneous dissemination of this virus.

• References

• 1 Plachter B, Sinzger C, Jahn G. Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 1996; 46: 195-261.
  PubMedGoogle Scholar
• 2 Sinzger C, Digel M, Jahn G. Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 2008; 325: 63-83.
  PubMedGoogle Scholar
• 3 Bissinger AL, Sinzger C, Kaiserling E. et al. 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 2002; 67: 200-206.
  CrossrefPubMedGoogle Scholar
• 4 Schafer P, Tenschert W, Cremaschi L. et al. Cytomegalovirus cultured from different major leukocyte subpopulations: association with clinical features in CMV immunoglobulin G-positive renal allograft recipients. J med Virol 2000; 61: 488-496.
  CrossrefPubMedGoogle Scholar
• 5 Gilbert GL, Hayes K, Hudson IL. et al. Prevention of transfusion-acquired cytomegalovirus infection in infants by blood filtration to remove leucocytes. Neonatal Cytomegalovirus Infection Study Group. Lancet 1989; 01: 1228-1231.
  PubMedGoogle Scholar
• 6 Grefte A, Harmsen MC, van der GM. et al. 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 1994; 75: 1989-1998.
  CrossrefPubMedGoogle Scholar
• 7 Grundy JE, Lawson KM, MacCormac LP. et al. Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell contact and during neutrophil transendothelial migration. J Infect Dis 1998; 177: 1465-1474.
  CrossrefPubMedGoogle Scholar
• 8 Ibanez CE, Schrier R, Ghazal P. et al. Human cytomegalovirus productively infects primary differentiated macrophages. J Virol 1991; 65: 6581-6588.
  PubMedGoogle Scholar
• 9 Lathey JL, Wiley CA, Verity MA. et al. Cultured human brain capillary endothelial cells are permissive for infection by human cytomegalovirus. Virology 1990; 176: 266-273.
  CrossrefPubMedGoogle Scholar
• 10 Sinzger C, Plachter B, Grefte A. et al. Tissue macrophages are infected by human cytomegalovirus in vivo. J Infect Dis 1996; 173: 240-245.
  CrossrefPubMedGoogle Scholar
• 11 Grefte A, Blom N, van der GM. et al. Ultrastructural analysis of circulating cytomegalic cells in patients with active cytomegalovirus infection: evidence for virus production and endothelial origin. J Infect Dis 1993; 168: 1110-1118.
  CrossrefPubMedGoogle Scholar
• 12 Percivalle E, Revello MG, Vago L. et al. Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement. J Clin Invest 1993; 92: 663-670.
  CrossrefPubMedGoogle Scholar
• 13 Sinzger C, Grefte A, Plachter B. et al. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 1995; 76: 741-750.
  CrossrefPubMedGoogle Scholar
• 14 Digel M, Sinzger C. Determinants of endothelial cell tropism of human cytomegalovirus. Cytomegaloviruses: Molecular Biology and Immunology. Caister Academic Press; 2006: 445-464.
  Google Scholar
• 15 Myerson D, Hackman RC, Nelson JA. et al. Widespread presence of histologically occult cytomegalovirus. Hum Pathol 1984; 15: 430-439.
  CrossrefPubMedGoogle Scholar
• 16 Roberts WH, Sneddon JM, Waldman J. et al. Cytomegalovirus infection of gastrointestinal endothelium demonstrated by simultaneous nucleic acid hybridization and immunohistochemistry. Arch Pathol Lab Med 1989; 113: 461-464.
  PubMedGoogle Scholar
• 17 Grefte A, van der GM, van Son W. et al. Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis 1993; 167: 270-277.
  CrossrefPubMedGoogle Scholar
• 18 Maidji E, Percivalle E, Gerna G. et al. Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts. Virol 2002; 304: 53-69.
  CrossrefPubMedGoogle Scholar
• 19 Hendrix MG, Dormans PH, Kitslaar P. et al. The presence of cytomegalovirus nucleic acids in arterial walls of atherosclerotic and nonatherosclerotic patients. Am J Pathol 1989; 134: 1151-1157.
  PubMedGoogle Scholar
• 20 Melnick JL, Petrie BL, Dreesman GR. et al. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet 1983; 02: 644-647.
  PubMedGoogle Scholar
• 21 Melnick JL, Hu C, Burek J. et al. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J med Virol 1994; 42: 170-174.
  CrossrefPubMedGoogle Scholar
• 22 Reeves MB, Coleman H, Chadderton J. et al. Vascular endothelial and smooth muscle cells are unlikely to be major sites of latency of human cytomegalovirus in vivo. J Gen Virol 2004; 85: 3337-3341.
  CrossrefPubMedGoogle Scholar
• 23 Pampou SY, Gnedoy SN, Bystrevskaya VB. et al. Cytomegalovirus genome and the immediate-early antigen in cells of different layers of human aorta. Virchows Arch 2000; 436: 539-552.
  CrossrefPubMedGoogle Scholar
• 24 Hendrix RM, Wagenaar M, Slobbe RL. et al. Widespread presence of cytomegalovirus DNA in tissues of healthy trauma victims. J Clin Pathol 1997; 50: 59-63.
  CrossrefPubMedGoogle Scholar
• 25 Jarvis MA, Nelson JA. Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. J Virol 2007; 81: 2095-2101.
  CrossrefPubMedGoogle Scholar
• 26 Lautenschlager I, Hockerstedt K, Taskinen E. et al. Expression of adhesion molecules and their ligands in liver allografts during cytomegalovirus (CMV) infection and acute rejection. Transpl Int 1996; 09 (Suppl. 01) S213-S215.
  CrossrefPubMedGoogle Scholar
• 27 Maisch T, Kropff B, Sinzger C. et al. Upregulation of CD40 expression on endothelial cells infected with human cytomegalovirus. J Virol 2002; 76: 12803-12812.
  CrossrefPubMedGoogle Scholar
• 28 Shahgasempour S, Woodroffe SB, Garnett HM. Alterations in the expression of ELAM-1, ICAM-1 and VCAM-1 after in vitro infection of endothelial cells with a clinical isolate of human cytomegalovirus. Microbiol Immunol 1997; 41: 121-129.
  CrossrefPubMedGoogle Scholar
• 29 Sedmak DD, Knight DA, Vook NC. et al. Divergent patterns of ELAM-1, ICAM-1, and VCAM-1 expression on cytomegalovirus-infected endothelial cells. Transplantation 1994; 58: 1379-1385.
  PubMedGoogle Scholar
• 30 Dengler TJ, Raftery MJ, Werle M. et al. Cytomegalovirus infection of vascular cells induces expression of pro-inflammatory adhesion molecules by paracrine action of secreted interleukin-1beta. Transplantation 2000; 69: 1160-1168.
  CrossrefPubMedGoogle Scholar
• 31 Rahbar A, Soderberg-Naucler C. Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation. J Virol 2005; 79: 2211-2220.
  CrossrefPubMedGoogle Scholar
• 32 Waldman WJ, Knight DA, Huang EH. et al. Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model. J Infect Dis 1995; 171: 263-272.
  CrossrefPubMedGoogle Scholar
• 33 Bentz GL, Jarquin-Pardo M, Chan G. et al. Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J Virol 2006; 80: 11539-11555.
  CrossrefPubMedGoogle Scholar
• 34 Bentz GL, Yurochko AD. Human CMV infection of endothelial cells induces an angiogenic response through viral binding to EGF receptor and beta1 and beta3 integrins. Proc Natl Acad Sci U S A 2008; 105: 5531-5536.
  CrossrefPubMedGoogle Scholar
• 35 Dumortier J, Streblow DN, Moses AV. et al. Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. J Virol 2008; 82: 6524-6535.
  CrossrefPubMedGoogle Scholar
• 36 Lijfering WM, de Vries AP, Veeger NJ. et al. Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation. Thromb Haemost 2008; 99: 127-132.
  Article in Thieme ConnectPubMedGoogle Scholar
• 37 Gueddi S, Righini M, Mezger N. et al. Portal vein thrombosis following a primary cytomegalovirus infection in an immunocompetent adult. Thromb Haemost 2006; 95: 199-201.
  Article in Thieme ConnectPubMedGoogle Scholar
• 38 Valantine HA. The role of viruses in cardiac allograft vasculopathy. Am J Transplant 2004; 04: 169-177.
  CrossrefPubMedGoogle Scholar
• 39 Merigan TC, Renlund DG, Keay S. et al. A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation. N Engl J Med 1992; 326: 1182-1186.
  CrossrefPubMedGoogle Scholar
• 40 Potena L, Holweg CT, Chin C. et al. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation 2006; 82: 398-405.
  PubMedGoogle Scholar
• 41 Chen R, Xiong S, Yang Y. et al. The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 2003; 249: 91-96.
  CrossrefPubMedGoogle Scholar
• 42 Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link?. Lancet 1997; 350: 430-436.
  CrossrefPubMedGoogle Scholar
• 43 Borgia MC, Mandolini C, Barresi C. et al. Further evidence against the implication of active cytomegalovirus infection in vascular atherosclerotic diseases. Atherosclerosis 2001; 157: 457-462.
  CrossrefPubMedGoogle Scholar
• 44 Nerheim PL, Meier JL, Vasef MA. et al. Enhanced cytomegalovirus infection in atherosclerotic human blood vessels. Am J Pathol 2004; 164: 589-600.
  CrossrefPubMedGoogle Scholar
• 45 Tumilowicz JJ, Gawlik ME, Powell BB. et al. Replication of cytomegalovirus in human arterial smooth muscle cells. J Virol 1985; 56: 839-845.
  PubMedGoogle Scholar
• 46 Tugizov S, Maidji E, Pereira L. Role of apical and basolateral membranes in replication of human cytomegalovirus in polarized retinal pigment epithelial cells. J Gen Virol 1996; 77: 61-74.
  CrossrefPubMedGoogle Scholar
• 47 Halwachs-Baumann G, Wilders-Truschnig M, Desoye G. et al. Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus. J Virol 1998; 72: 7598-7602.
  PubMedGoogle Scholar
• 48 Sinzger C, Bissinger AL, Viebahn R. et al. Hepatocytes are permissive for human cytomegalovirus infection in human liver cell culture and In vivo. J Infect Dis 1999; 180: 976-986.
  CrossrefPubMedGoogle Scholar
• 49 Poland SD, Costello P, Dekaban GA. et al. GP. Cytomegalovirus in the brain: in vitro infection of human brain-derived cells. J Infect Dis 1990; 162: 1252-1262.
  CrossrefPubMedGoogle Scholar
• 50 Heieren MH, Kim YK, Balfour Jr HH. Human cytomegalovirus infection of kidney glomerular visceral epithelial and tubular epithelial cells in culture. Transplantation 1988; 46: 426-432.
  CrossrefPubMedGoogle Scholar
• 51 Riegler S, Hebart H, Einsele H. et al. Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus. J Gen Virol 2000; 81: 393-399.
  CrossrefPubMedGoogle Scholar
• 52 Ho DD, Rota TR, Andrews CA. et al. Replication of human cytomegalovirus in endothelial cells. J Infect Dis 1984; 150: 956-957.
  CrossrefPubMedGoogle Scholar
• 53 Waldman WJ, Sneddon JM, Stephens RE, Roberts WH. Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells. J med Virol 1989; 28: 223-30.
  CrossrefPubMedGoogle Scholar
• 54 Kahl M, Siegel-Axel D, Stenglein S. et al. Efficient lytic infection of human arterial endothelial cells by human cytomegalovirus strains. J Virol 2000; 74: 7628-7635.
  CrossrefPubMedGoogle Scholar
• 55 Knight DA, Waldman WJ, Sedmak DD. Cytomegalovirus-mediated modulation of adhesion molecule expression by human arterial and microvascular endothelial cells. Transplantation 1999; 68: 1814-1818.
  CrossrefPubMedGoogle Scholar
• 56 Sindre H, Haraldsen G, Beck S. et al. Human intestinal endothelium shows high susceptibility to cytomegalovirus and altered expression of adhesion molecules after infection. Scand J Immunol 2000; 51: 354-360.
  CrossrefPubMedGoogle Scholar
• 57 Ustinov JA, Loginov RJ, Mattila PM. et al. Cytomegalovirus infection of human kidney cells in vitro. Kidney Int 1991; 40: 954-960.
  PubMedGoogle Scholar
• 58 Conway EM, Carmeliet P. The diversity of endothelial cells: a challenge for therapeutic angiogenesis. Genome Biol 2004; 05: 207.
  CrossrefPubMedGoogle Scholar
• 59 Chi JT, Chang HY, Haraldsen G. et al. Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A 2003; 100: 10623-10628.
  CrossrefPubMedGoogle Scholar
• 60 Kallmann BA, Wagner S, Hummel V. et al. Characteristic gene expression profile of primary human cerebral endothelial cells. FASEB J 2002; 16: 589-591.
  CrossrefPubMedGoogle Scholar
• 61 Waldman WJ, Knight DA, Huang EH. et al. Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model. J Infect Dis 1995; 171: 263-272.
  CrossrefPubMedGoogle Scholar
• 62 Sinzger C, Knapp J, Plachter B. et al. Quantification of replication of clinical cytomegalovirus isolates in cultured endothelial cells and fibroblasts by a focus expansion assay. J Virol Methods 1997; 63: 103-112.
  CrossrefPubMedGoogle Scholar
• 63 Sinzger C, Schmidt K, Knapp J. et al. Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome. J Gen Virol 1999; 80: 2867-2877.
  CrossrefPubMedGoogle Scholar
• 64 Grazia RM, Baldanti F, Percivalle E. et al. In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells. J Gen Virol 2001; 82: 1429-1438.
  CrossrefPubMedGoogle Scholar
• 65 Gerna G, Sarasini A, Genini E. et al. Prediction of endothelial cell tropism of human cytomegalovirus strains. J Clin Virol 2006; 35: 470-473.
  CrossrefPubMedGoogle Scholar
• 66 MacCormac LP, Grundy JE. Two clinical isolates and the Toledo strain of cytomegalovirus contain endothelial cell tropic variants that are not present in the AD169, Towne, or Davis strains. J med Virol 1999; 57: 298-307.
  CrossrefPubMedGoogle Scholar
• 67 Gerna G, Percivalle E, Sarasini A. et al. The attenuated Towne strain of human cytomegalovirus may revert to both endothelial cell tropism and leuko- (neutrophiland monocyte-) tropism in vitro. J Gen Virol 2002; 83: 1993-2000.
  CrossrefPubMedGoogle Scholar
• 68 Gerna G, Percivalle E, Sarasini A. et al. Rescue of human cytomegalovirus strain AD169 tropism for both leukocytes and human endothelial cells. J Gen Virol 2003; 84: 1431-1436.
  CrossrefPubMedGoogle Scholar
• 69 Sinzger C, Hahn G, Digel M. et al. Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E. J Gen Virol 2008; 89: 359-368.
  CrossrefPubMedGoogle Scholar
• 70 Baldanti F, Revello MG, Percivalle E. et al. Genomes of the endothelial cell-tropic variant and the parental Toledo strain of human cytomegalovirus are highly divergent. J med Virol 2003; 69: 76-81.
  CrossrefPubMedGoogle Scholar
• 71 Prichard MN, Penfold ME, Duke GM. et al. A review of genetic differences between limited and extensively passaged human cytomegalovirus strains. Rev Med Virol 2001; 11: 191-200.
  CrossrefPubMedGoogle Scholar
• 72 Cha TA, Tom E, Kemble GW. et al. Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J Virol 1996; 70: 78-83.
  PubMedGoogle Scholar
• 73 Akter P, Cunningham C, McSharry BP. et al. Two novel spliced genes in human cytomegalovirus. J Gen Virol 2003; 84: 1117-1122.
  CrossrefPubMedGoogle Scholar
• 74 Hahn G, Revello MG, Patrone M. et al. Human cytomegalovirus UL131–128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 2004; 78: 10023-10033.
  CrossrefPubMedGoogle Scholar
• 75 Ryckman BJ, Jarvis MA, Drummond DD. et al. Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 2006; 80: 710-722.
  CrossrefPubMedGoogle Scholar
• 76 Baldanti F, Paolucci S, Campanini G. et al. Human cytomegalovirus UL131A, UL130 and UL128 genes are highly conserved among field isolates. Arch Virol 2005; 105: 1225-1233.
  PubMedGoogle Scholar
• 77 Messerle M, Crnkovic I, Hammerschmidt W. et al. Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc Natl Acad Sci USA 1997; 94: 14759-14763.
  CrossrefPubMedGoogle Scholar
• 78 Borst E-M, Hahn G, Koszinowski UH. et al. Cloning of the Human Cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J Virol 1999; 73: 8320-8329.
  PubMedGoogle Scholar
• 79 Hahn G, Khan H, Baldanti F. et al. 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 2002; 76: 9551-9555.
  CrossrefPubMedGoogle Scholar
• 80 Murphy E, Yu D, Grimwood J. et al. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 2003; 100: 14976-14981.
  CrossrefPubMedGoogle Scholar
• 81 Dunn W, Chou C, Li H. et al. Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci U S A 2003; 100: 14223-14228.
  CrossrefPubMedGoogle Scholar
• 82 Wang D, Shenk T. Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J Virol 2005; 79: 10330-10338.
  CrossrefPubMedGoogle Scholar
• 83 Adler B, Scrivano L, Ruzcics Z. et al. Role of human cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol 2006; 87: 2451-2460.
  CrossrefPubMedGoogle Scholar
• 84 Wang D, Shenk T. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 2005; 102: 18153-18158.
  CrossrefPubMedGoogle Scholar
• 85 Patrone M, Secchi M, Fiorina L. et al. Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J Virol 2005; 79: 8361-8373.
  CrossrefPubMedGoogle Scholar
• 86 Huber MT, Compton T. The human cytomegalovirus UL74 gene encodes the third component of the glycoprotein H-glycoprotein L-containing envelope complex. J Virol 1998; 72: 8191-8197.
  PubMedGoogle Scholar
• 87 Li L, Nelson JA, Britt WJ. Glycoprotein H-related complexes of human cytomegalovirus: identification of a third protein in the gCIII complex. J Virol 1997; 71: 3090-3097.
  PubMedGoogle Scholar
• 88 Jiang XJ, Adler B, Sampaio KL. et al. UL74 of human cytomegalovirus contributes to virus release by promoting secondary envelopment of virions. J Virol 2008; 82: 2802-2812.
  CrossrefPubMedGoogle Scholar
• 89 Gerna G, Percivalle E, Lilleri D. et al. Dendriticcell infection by human cytomegalovirus is restricted to strains carrying functional UL131–128 genes and mediates efficient viral antigen presentation to CD8+ T cells. J Gen Virol 2005; 86: 275-284.
  CrossrefPubMedGoogle Scholar
• 90 Spear PG, Longnecker R. Herpesvirus entry: an update. J Virol 2003; 77: 10179-10185.
  CrossrefPubMedGoogle Scholar
• 91 Mori Y, Yang X, Akkapaiboon P. et al. Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q complex associates with human CD46. J Virol 2003; 77: 4992-4999.
  CrossrefPubMedGoogle Scholar
• 92 Kirschner AN, Lowrey AS, Longnecker R. et al. Binding-site interactions between Epstein-Barr virus fusion proteins gp42 and gH/gL reveal a peptide that inhibits both epithelial and B-cell membrane fusion. J Virol 2007; 81: 9216-9229.
  CrossrefPubMedGoogle Scholar
• 93 Hutt-Fletcher LM. Epstein-Barr virus entry. J Virol 2007; 81: 7825-7832.
  CrossrefPubMedGoogle Scholar
• 94 Mori Y, Akkapaiboon P, Yonemoto S. et al. Discovery of a second form of tripartite complex containing gH-gL of human herpesvirus 6 and observations on CD46. J Virol 2004; 78: 4609-4616.
  CrossrefPubMedGoogle Scholar
• 95 Borza CM, Hutt-Fletcher LM. Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med 2002; 08: 594-599.
  CrossrefPubMedGoogle Scholar
• 96 Reinhardt B, Vaida B, Voisard R. et al. Human cytomegalovirus infection in human renal arteries in vitro. J Virol Methods 2003; 109: 1-9.
  CrossrefPubMedGoogle Scholar
• 97 Maidji E, Genbacev O, Chang HT. et al. Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta. J Virol 2007; 81: 4701-4712.
  CrossrefPubMedGoogle Scholar
• 98 Keay S, Baldwin B. The human fibroblast receptor for gp86 of human cytomegalovirus is a phosphorylated glycoprotein. J Virol 1992; 66: 4834-4838.
  PubMedGoogle Scholar
• 99 Wright JF, Kurosky A, Wasi S. An endothelial cellsurface form of annexin II binds human cytomegalovirus. Biochem Biophys Res Commun 1994; 198: 983-989.
  CrossrefPubMedGoogle Scholar
• 100 Pietropaolo RL, Compton T. Direct interaction between human cytomegalovirus glycoprotein B and cellular annexin II. J Virol 1997; 71: 9803-9807.
  PubMedGoogle Scholar
• 101 Pietropaolo R, Compton T. Interference with annexin II has no effect on entry of human cytomegalovirus into fibroblast cells. J Gen Virol 1999; 80: 1807-1816.
  CrossrefPubMedGoogle Scholar
• 102 Soderberg C, Giugni TD, Zaia JA. et al. CD13 (human aminopeptidase N) mediates human cytomegalovirus infection. J Virol 1993; 67: 6576-6585.
  PubMedGoogle Scholar
• 103 Wang X, Huong SM, Chiu ML. et al. Epidermal growth factor receptor is a cellular receptor for human cytomegalovirus. Nature 2003; 424: 456-461.
  CrossrefPubMedGoogle Scholar
• 104 Soroceanu L, Akhavan A, Cobbs CS. Platelet-derived growth factor-alpha receptor activation is required for human cytomegalovirus infection. Nature 2008; 455: 391-395.
  CrossrefPubMedGoogle Scholar
• 105 Isaacson MK, Feire AL, Compton T. Epidermal growth factor receptor is not required for human cytomegalovirus entry or signaling. J Virol 2007; 81: 6241-6247.
  CrossrefPubMedGoogle Scholar
• 106 Wang X, Huang DY, Huong SM. et al. Integrin alphavbeta3 is a coreceptor for human cytomegalovirus. Nat Med 2005; 11: 515-521.
  CrossrefPubMedGoogle Scholar
• 107 Miller N, Hutt-Fletcher LM. Epstein-Barr virus enters B cells and epithelial cells by different routes. J Virol 1992; 66: 3409-3414.
  PubMedGoogle Scholar
• 108 Nicola AV, McEvoy AM, Straus SE. Roles for endocytosis and low pH in herpes simplex virus entry into HeLa and Chinese hamster ovary cells. J Virol 2003; 77: 5324-5332.
  CrossrefPubMedGoogle Scholar
• 109 Nicola AV, Hou J, Major EO. et al. Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway. J Virol 2005; 79: 7609-7616.
  CrossrefPubMedGoogle Scholar
• 110 Milne RS, Nicola AV, Whitbeck JC. et al. Glycoprotein D receptor-dependent, low-pH-independent endocytic entry of herpes simplex virus type 1. J Virol 2005; 79: 6655-6663.
  CrossrefPubMedGoogle Scholar
• 111 Akula SM, Naranatt PP, Walia NS. et al. Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) infection of human fibroblast cells occurs through endocytosis. J Virol 2003; 77: 7978-7990.
  CrossrefPubMedGoogle Scholar
• 112 Bodaghi B, Slobbe-van Drunen ME. et al. Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest Ophthalmol Vis Sci 1999; 40: 2598-2607.
  PubMedGoogle Scholar
• 113 Sinzger C. Entry route of HCMV into endothelial cells. J Clin Virol 2008; 41: 174-179.
  CrossrefPubMedGoogle Scholar
• 114 Smith JD, de Harven E. Herpes simplex virus and human cytomegalovirus replication in WI-38 cells. II. An ultrastructural study of viral penetration. J Virol 1974; 14: 945-956.
  PubMedGoogle Scholar
• 115 Patrone M, Secchi M, Bonaparte E. et al. Cytomegalovirus UL131–128 products promote gB conformational transition and gB-gH interaction during entry into endothelial cells. J Virol 2007; 81: 11479-11488.
  CrossrefPubMedGoogle Scholar
• 116 Wang D, Yu QC, Schroer J. et al. Human cytomegalovirus uses two distinct pathways to enter retinal pigmented epithelial cells. Proc Natl Acad Sci U S A 2007; 104: 20037-20042.
  CrossrefPubMedGoogle Scholar
• 117 Halary F, Amara A, Lortat-Jacob H. et al. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity 2002; 17: 653-664.
  CrossrefPubMedGoogle Scholar
• 118 Mocarski Jr ES, Kemble GW. Recombinant cytomegaloviruses for study of replication and pathogenesis. Intervirology 1996; 39: 320-330.
  CrossrefPubMedGoogle Scholar
• 119 Krmpotic A, Bubic I, Polic B. et al. Pathogenesis of murine cytomegalovirus infection. Microbes Infect 2003; 05: 1263-1277.
  CrossrefPubMedGoogle Scholar
• 120 Reddehase MJ, Podlech J, Grzimek NK. Mouse models of cytomegalovirus latency: overview. J Clin Virol 2002; 25 (Suppl. 02) S23-36.
  PubMedGoogle Scholar
• 121 Schnee M, Ruzsics Z, Bubeck A. et al. Common and specific properties of herpesvirus UL34/UL31 protein family members revealed by protein complementation assay. J Virol 2006; 80: 11658-11666.
  CrossrefPubMedGoogle Scholar
• 122 Sacher T, Podlech J, Mohr CA. et al. The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 2008; 03: 263-272.
  CrossrefPubMedGoogle Scholar