1887

Abstract

Cytomegaloviruses (CMVs) are large, complex pathogens that persistently and systemically colonize most mammals. Human cytomegalovirus (HCMV) causes congenital harm, and has proved hard to control. One problem is that key vaccine targets – virus entry and spread in naive hosts – remain ill-defined. As CMVs predate human speciation, those of other mammals can provide new insight. Murine CMV (MCMV) enters new hosts via olfactory neurons. Like HCMV it binds to heparan, which is lacking from most differentiated apical epithelia but is displayed on olfactory neuronal cilia. It then spreads via infected dendritic cells (DCs), which migrate to draining lymph nodes (LNs), rejoin the circulation by entering high endothelial venules (HEVs), and extravasate into other tissues. This migration depends quantitatively on M33, a constitutively active viral G protein-coupled receptor (GPCR). The homologous US28 GPCR of HCMV can substitute for M33 in allowing MCMV-infected DCs to leave LNs via HEVs, so HCMV could potentially use the same route. The capacity of DCs to seed MCMV to tissues, and for other DCs to collect it for redistribution, suggest that DC recirculation chronically maintains and links diverse CMV reservoirs through lytic exchange.

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2019-02-07
2019-09-23
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References

  1. Weller TH. The cytomegaloviruses: ubiquitous agents with protean clinical manifestations. II. N Engl J Med 1971;285:267–274 [CrossRef][PubMed]
    [Google Scholar]
  2. Plachter B. Prospects of a vaccine for the prevention of congenital cytomegalovirus disease. Med Microbiol Immunol 2016;205:537–547 [CrossRef][PubMed]
    [Google Scholar]
  3. Davison AJ. Evolution of sexually transmitted and sexually transmissible human herpesviruses. Ann N Y Acad Sci 2011;1230:E37E49 [CrossRef][PubMed]
    [Google Scholar]
  4. Stagno S, Reynolds DW, Pass RF, Alford CA. Breast milk and the risk of cytomegalovirus infection. N Engl J Med 1980;302:1073–1076 [CrossRef][PubMed]
    [Google Scholar]
  5. Pass RF, Hutto C, Ricks R, Cloud GA. Increased rate of cytomegalovirus infection among parents of children attending day-care centers. N Engl J Med 1986;314:1414–1418 [CrossRef][PubMed]
    [Google Scholar]
  6. Omari TI, Davidson GP. Multipoint measurement of intragastric pH in healthy preterm infants. Arch Dis Child Fetal Neonatal Ed 2003;88:517F–520 [CrossRef][PubMed]
    [Google Scholar]
  7. Mayer BT, Krantz EM, Swan D, Ferrenberg J, Simmons K et al. Transient oral human cytomegalovirus infections indicate inefficient viral spread from very few initially infected cells. J Virol 2017;91:e00380 [CrossRef][PubMed]
    [Google Scholar]
  8. Turtinen LW, Saltzman R, Jordan MC, Haase AT. Interactions of human cytomegalovirus with leukocytes in vivo: analysis by in situ hybridization. Microb Pathog 1987;3:287–297 [CrossRef][PubMed]
    [Google Scholar]
  9. Taylor-Wiedeman J, Sissons JGP, Borysiewicz LK, Sinclair JH. Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol 1991;72:2059–2064 [CrossRef]
    [Google Scholar]
  10. Sinclair J, Reeves M. The intimate relationship between human cytomegalovirus and the dendritic cell lineage. Front Microbiol 2014;5:389 [CrossRef][PubMed]
    [Google Scholar]
  11. Crawford LB, Streblow DN, Hakki M, Nelson JA, Caposio P. Humanized mouse models of human cytomegalovirus infection. Curr Opin Virol 2015;13:86–92 [CrossRef][PubMed]
    [Google Scholar]
  12. Mcgeoch DJ, Rixon FJ, Davison AJ. Topics in herpesvirus genomics and evolution. Virus Res 2006;117:90–104 [CrossRef][PubMed]
    [Google Scholar]
  13. Wilkie GS, Davison AJ, Watson M, Kerr K, Sanderson S et al. Complete genome sequences of elephant endotheliotropic herpesviruses 1A and 1B determined directly from fatal cases. J Virol 2013;87:6700–6712 [CrossRef][PubMed]
    [Google Scholar]
  14. Yewdell JW, Hill AB. Viral interference with antigen presentation. Nat Immunol 2002;3:1019–1025 [CrossRef][PubMed]
    [Google Scholar]
  15. Hume DA, Freeman TC. Transcriptomic analysis of mononuclear phagocyte differentiation and activation. Immunol Rev 2014;262:74–84 [CrossRef][PubMed]
    [Google Scholar]
  16. Lang DJ, Garruto RM, Gajdusek DC. Early acquisition of cytomegalovirus and Epstein-Barr virus antibody in several isolated Melanesian populations. Am J Epidemiol 1977;105:480–487 [CrossRef][PubMed]
    [Google Scholar]
  17. Powers C, Früh K. Rhesus CMV: an emerging animal model for human CMV. Med Microbiol Immunol 2008;197:109–115 [CrossRef][PubMed]
    [Google Scholar]
  18. Schleiss MR. Animal models of congenital cytomegalovirus infection: an overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV). J Clinical Virol 2002;25:37–49 [CrossRef]
    [Google Scholar]
  19. Pass RF, Hutto SC, Reynolds DW, Polhill RB. Increased frequency of cytomegalovirus infection in children in group day care. Pediatrics 1984;74:121–126[PubMed]
    [Google Scholar]
  20. Tan CS, Frederico B, Stevenson PG. Herpesvirus delivery to the murine respiratory tract. J Virol Methods 2014;206:105–114 [CrossRef][PubMed]
    [Google Scholar]
  21. Wu CA, Paveglio SA, Lingenheld EG, Zhu L, Lefrançois L et al. Transmission of murine cytomegalovirus in breast milk: a model of natural infection in neonates. J Virol 2011;85:5115–5124 [CrossRef][PubMed]
    [Google Scholar]
  22. Stahl FR, Heller K, Halle S, Keyser KA, Busche A et al. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung. PLoS Pathog 2013;9:e1003828 [CrossRef][PubMed]
    [Google Scholar]
  23. Farrell HE, Lawler C, Tan CS, Macdonald K, Bruce K et al. Murine cytomegalovirus exploits olfaction to enter new hosts. mBio 2016;7:e00251 [CrossRef][PubMed]
    [Google Scholar]
  24. Lockridge KM, Sequar G, Zhou SS, Yue Y, Mandell CP et al. Pathogenesis of experimental rhesus cytomegalovirus infection. J Virol 1999;73:9576–9583[PubMed]
    [Google Scholar]
  25. Milho R, Frederico B, Efstathiou S, Stevenson PG. A heparan-dependent herpesvirus targets the olfactory neuroepithelium for host entry. PLoS Pathog 2012;8:e1002986 [CrossRef][PubMed]
    [Google Scholar]
  26. Shivkumar M, Milho R, May JS, Nicoll MP, Efstathiou S et al. Herpes simplex virus 1 targets the murine olfactory neuroepithelium for host entry. J Virol 2013;87:10477–10488 [CrossRef][PubMed]
    [Google Scholar]
  27. Xiang J, Zhang S, Nauwynck H. Infections of neonatal and adult mice with murine CMV HaNa1 strain upon oronasal inoculation: New insights in the pathogenesis of natural primary CMV infections. Virus Res 2016;211:96–102 [CrossRef][PubMed]
    [Google Scholar]
  28. Compton T, Nowlin DM, Cooper NR. Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate. Virology 1993;193:834–841 [CrossRef][PubMed]
    [Google Scholar]
  29. Chesnokova LS, Valencia SM, Hutt-Fletcher LM. The BDLF3 gene product of Epstein-Barr virus, gp150, mediates non-productive binding to heparan sulfate on epithelial cells and only the binding domain of CD21 is required for infection. Virology 2016;494:23–28 [CrossRef][PubMed]
    [Google Scholar]
  30. Feederle R, Neuhierl B, Bannert H, Geletneky K, Shannon-Lowe C et al. Epstein-Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection. Int J Cancer 2007;121:588–594 [CrossRef][PubMed]
    [Google Scholar]
  31. Hayashi K, Hayashi M, Jalkanen M, Firestone JH, Trelstad RL et al. Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem 1987;35:1079–1088 [CrossRef][PubMed]
    [Google Scholar]
  32. François S, Vidick S, Sarlet M, Desmecht D, Drion P et al. Illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice. PLoS Pathog 2013;9:e1003292 [CrossRef][PubMed]
    [Google Scholar]
  33. Collins TM, Quirk MR, Jordan MC. Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice. J Virol 1994;68:6305–6311[PubMed]
    [Google Scholar]
  34. Frederico B, Chao B, May JS, Belz GT, Stevenson PG. A murid gamma-herpesviruses exploits normal splenic immune communication routes for systemic spread. Cell Host Microbe 2014;15:457–470 [CrossRef][PubMed]
    [Google Scholar]
  35. Hsu KM, Pratt JR, Akers WJ, Achilefu SI, Yokoyama WM. Murine cytomegalovirus displays selective infection of cells within hours after systemic administration. J Gen Virol 2009;90:33–43 [CrossRef][PubMed]
    [Google Scholar]
  36. Farrell HE, Bruce K, Lawler C, Oliveira M, Cardin R et al. Murine cytomegalovirus spreads by dendritic cell recirculation. mBio 2017;8:e01264 [CrossRef][PubMed]
    [Google Scholar]
  37. Daley-Bauer LP, Roback LJ, Wynn GM, Mocarski ES. Cytomegalovirus hijacks CX3CR1(hi) patrolling monocytes as immune-privileged vehicles for dissemination in mice. Cell Host Microbe 2014;15:351–362 [CrossRef][PubMed]
    [Google Scholar]
  38. Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity 2014;41:21–35 [CrossRef][PubMed]
    [Google Scholar]
  39. Farrell HE, Bruce K, Lawler C, Cardin RD, Davis-Poynter NJ et al. Type 1 interferons and nk cells limit murine cytomegalovirus escape from the lymph node subcapsular sinus. PLoS Pathog 2016;12:e1006069 [CrossRef][PubMed]
    [Google Scholar]
  40. Farrell HE, Davis-Poynter N, Bruce K, Lawler C, Dolken L et al. Lymph node macrophages restrict murine cytomegalovirus dissemination. J Virol 2015;89:7147–7158 [CrossRef][PubMed]
    [Google Scholar]
  41. Farrell HE, Lawler C, Oliveira MT, Davis-Poynter N, Stevenson PG. Alveolar macrophages are a prominent but nonessential target for murine cytomegalovirus infecting the lungs. J Virol 2015;90:2756–2766 [CrossRef][PubMed]
    [Google Scholar]
  42. Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol 2005;5:617–628 [CrossRef][PubMed]
    [Google Scholar]
  43. Gesner BM, Gowans JL. The output of lymphocytes from the thoracic duct of unanaesthetized mice. Br J Exp Pathol 1962;43:424–430[PubMed]
    [Google Scholar]
  44. Förster R, Braun A, Worbs T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol 2012;33:271–280 [CrossRef][PubMed]
    [Google Scholar]
  45. Davis-Poynter NJ, Lynch DM, Vally H, Shellam GR, Rawlinson WD et al. Identification and characterization of a G protein-coupled receptor homolog encoded by murine cytomegalovirus. J Virol 1997;71:1521–1529[PubMed]
    [Google Scholar]
  46. Beisser PS, Vink C, van Dam JG, Grauls G, Vanherle SJ et al. The R33 G protein-coupled receptor gene of rat cytomegalovirus plays an essential role in the pathogenesis of viral infection. J Virol 1998;72:2352–2363[PubMed]
    [Google Scholar]
  47. Rawlinson WD, Farrell HE, Barrell BG. Analysis of the complete DNA sequence of murine cytomegalovirus. J Virol 1996;70:8833–8849[PubMed]
    [Google Scholar]
  48. Gruijthuijsen YK, Casarosa P, Kaptein SJ, Broers JL, Leurs R et al. The rat cytomegalovirus R33-encoded G protein-coupled receptor signals in a constitutive fashion. J Virol 2002;76:1328–1338 [CrossRef][PubMed]
    [Google Scholar]
  49. Waldhoer M, Kledal TN, Farrell H, Schwartz TW. Murine cytomegalovirus (CMV) M33 and human CMV US28 receptors exhibit similar constitutive signaling activities. J Virol 2002;76:8161–8168 [CrossRef][PubMed]
    [Google Scholar]
  50. Mølleskov-Jensen AS, Oliveira MT, Farrell HE, Davis-Poynter N. In Klasse PJ. (editor) Progress in Molecular Biology and Translational Sciencevol. 129 Burlington: Academic Press; 2015; pp.353–393
    [Google Scholar]
  51. Case R, Sharp E, Benned-Jensen T, Rosenkilde MM, Davis-Poynter N et al. Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo. J Virol 2008;82:1884–1898 [CrossRef][PubMed]
    [Google Scholar]
  52. Cardin RD, Schaefer GC, Allen JR, Davis-Poynter NJ, Farrell HE. The M33 chemokine receptor homolog of murine cytomegalovirus exhibits a differential tissue-specific role during in vivo replication and latency. J Virol 2009;83:7590–7601 [CrossRef][PubMed]
    [Google Scholar]
  53. Bittencourt FM, Wu SE, Bridges JP, Miller WE. The M33 G protein-coupled receptor encoded by murine cytomegalovirus is dispensable for hematogenous dissemination but is required for growth within the salivary gland. J Virol 2014;88:11811–11824 [CrossRef][PubMed]
    [Google Scholar]
  54. Oliveira SA, Shenk TE. Murine cytomegalovirus M78 protein, a G protein-coupled receptor homologue, is a constituent of the virion and facilitates accumulation of immediate-early viral mRNA. Proc Natl Acad Sci USA 2001;98:3237–3242 [CrossRef][PubMed]
    [Google Scholar]
  55. Yunis J, Farrell HE, Bruce K, Lawler C, Sidenius S et al. Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. PLoS Pathog 2018;14:e1006905 [CrossRef][PubMed]
    [Google Scholar]
  56. Penfold ME, Schmidt TL, Dairaghi DJ, Barry PA, Schall TJ. Characterization of the rhesus cytomegalovirus US28 locus. J Virol 2003;77:10404–10413 [CrossRef][PubMed]
    [Google Scholar]
  57. Kuhn DE, Beall CJ, Kolattukudy PE. The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem Biophys Res Commun 1995;211:325–330 [CrossRef][PubMed]
    [Google Scholar]
  58. Bodaghi B, Jones TR, Zipeto D, Vita C, Sun L et al. Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. J Exp Med 1998;188:855–866 [CrossRef][PubMed]
    [Google Scholar]
  59. Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E et al. The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell 1999;99:511–520 [CrossRef][PubMed]
    [Google Scholar]
  60. de Wit RH, Mujić-Delić A, van Senten JR, Fraile-Ramos A, Siderius M et al. Human cytomegalovirus encoded chemokine receptor US28 activates the HIF-1α/PKM2 axis in glioblastoma cells. Oncotarget 2016;7:67966–67985 [CrossRef][PubMed]
    [Google Scholar]
  61. Noriega VM, Gardner TJ, Redmann V, Bongers G, Lira SA et al. Human cytomegalovirus US28 facilitates cell-to-cell viral dissemination. Viruses 2014;6:1202–1218 [CrossRef][PubMed]
    [Google Scholar]
  62. Krishna BA, Poole EL, Jackson SE, Smit MJ, Wills MR et al. Latency-Associated expression of human cytomegalovirus us28 attenuates cell signaling pathways to maintain latent infection. MBio 2017;8:e01754 [CrossRef][PubMed]
    [Google Scholar]
  63. Maussang D, Verzijl D, van Walsum M, Leurs R, Holl J et al. Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis. Proc Natl Acad Sci USA 2006;103:13068–13073 [CrossRef][PubMed]
    [Google Scholar]
  64. Maussang D, Vischer HF, Leurs R, Smit MJ. Herpesvirus-encoded G protein-coupled receptors as modulators of cellular function. Mol Pharmacol 2009;76:692–701 [CrossRef][PubMed]
    [Google Scholar]
  65. Krishna BA, Spiess K, Poole EL, Lau B, Voigt S et al. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein. Nat Commun 2017;8:14321 [CrossRef][PubMed]
    [Google Scholar]
  66. Spiess K, Jeppesen MG, Malmgaard-Clausen M, Krzywkowski K, Dulal K et al. Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo. Proc Natl Acad Sci USA 2015;112:8427–8432 [CrossRef][PubMed]
    [Google Scholar]
  67. Bakker RA, Casarosa P, Timmerman H, Smit MJ, Leurs R. Constitutively active Gq/11-coupled receptors enable signaling by co-expressed G(i/o)-coupled receptors. J Biol Chem 2004;279:5152–5161 [CrossRef][PubMed]
    [Google Scholar]
  68. Tschische P, Tadagaki K, Kamal M, Jockers R, Waldhoer M. Heteromerization of human cytomegalovirus encoded chemokine receptors. Biochem Pharmacol 2011;82:610–619 [CrossRef][PubMed]
    [Google Scholar]
  69. Farrell HE, Bruce K, Ma J, Davis-Poynter N, Stevenson PG. Human cytomegalovirus US28 allows dendritic cell exit from lymph nodes. J Gen Virol 2018;99:1509–1514 [CrossRef][PubMed]
    [Google Scholar]
  70. Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 2014;14:392–404 [CrossRef][PubMed]
    [Google Scholar]
  71. Girard JP, Moussion C, Förster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol 2012;12:762–773 [CrossRef][PubMed]
    [Google Scholar]
  72. Hauser MA, Legler DF. Common and biased signaling pathways of the chemokine receptor CCR7 elicited by its ligands CCL19 and CCL21 in leukocytes. J Leukoc Biol 2016;99:869–882 [CrossRef][PubMed]
    [Google Scholar]
  73. Platt AM, Randolph GJ. Dendritic cell migration through the lymphatic vasculature to lymph nodes. Adv Immunol 2013;120:51–68 [CrossRef][PubMed]
    [Google Scholar]
  74. Pham TH, Okada T, Matloubian M, Lo CG, Cyster JG. S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress. Immunity 2008;28:122–133 [CrossRef][PubMed]
    [Google Scholar]
  75. Cyster JG, Schwab SR. Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu Rev Immunol 2012;30:69–94 [CrossRef][PubMed]
    [Google Scholar]
  76. Grigorova IL, Panteleev M, Cyster JG. Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure. Proc Natl Acad Sci USA 2010;107:20447–20452 [CrossRef][PubMed]
    [Google Scholar]
  77. Seckert CK, Renzaho A, Reddehase MJ, Grzimek NK. Hematopoietic stem cell transplantation with latently infected donors does not transmit virus to immunocompromised recipients in the murine model of cytomegalovirus infection. Med Microbiol Immunol 2008;197:251–259 [CrossRef][PubMed]
    [Google Scholar]
  78. Griffiths PD, Cope AV, Hassan-Walker AF, Emery VC. Diagnostic approaches to cytomegalovirus infection in bone marrow and organ transplantation. Transpl Infect Dis 1999;1:179–186 [CrossRef][PubMed]
    [Google Scholar]
  79. Pergam SA, Xie H, Sandhu R, Pollack M, Smith J et al. Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients. Biol Blood Marrow Transplant 2012;18:1391–1400 [CrossRef][PubMed]
    [Google Scholar]
  80. Boivin G, Quirk MR, Kringstad BA, Germain M, Jordan MC. Early effects of ganciclovir therapy on the quantity of cytomegalovirus DNA in leukocytes of immunocompromised patients. Antimicrob Agents Chemother 1997;41:860–862 [CrossRef][PubMed]
    [Google Scholar]
  81. Maciejewski JP, Bruening EE, Donahue RE, Mocarski ES, Young NS et al. Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood 1992;80:170–178[PubMed]
    [Google Scholar]
  82. Goodrum F, Jordan CT, Terhune SS, High K, Shenk T. Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood 2004;104:687–695 [CrossRef][PubMed]
    [Google Scholar]
  83. Smith MS, Goldman DC, Bailey AS, Pfaffle DL, Kreklywich CN et al. Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 2010;8:284–291 [CrossRef][PubMed]
    [Google Scholar]
  84. Hakki M, Goldman DC, Streblow DN, Hamlin KL, Krekylwich CN et al. HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors. Biol Blood Marrow Transplant 2014;20:132–135 [CrossRef][PubMed]
    [Google Scholar]
  85. Milho R, Smith CM, Marques S, Alenquer M, May JS et al. In vivo imaging of murid herpesvirus-4 infection. J Gen Virol 2009;90:21–32 [CrossRef][PubMed]
    [Google Scholar]
  86. Farrell H, Oliveira M, Macdonald K, Yunis J, Mach M et al. Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge. J Gen Virol 2016;97:3379–3391 [CrossRef][PubMed]
    [Google Scholar]
  87. Terry LA, Stewart JP, Nash AA, Fazakerley JK. Murine gammaherpesvirus-68 infection of and persistence in the central nervous system. J Gen Virol 2000;81:2635–2643 [CrossRef][PubMed]
    [Google Scholar]
  88. Mendelson M, Monard S, Sissons P, Sinclair J. Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 1996;77:3099–3102 [CrossRef][PubMed]
    [Google Scholar]
  89. von Laer D, Meyer-Koenig U, Serr A, Finke J, Kanz L et al. Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow. Blood 1995;86:4086–4090[PubMed]
    [Google Scholar]
  90. Larsson S, Söderberg-Nauclér C, Wang FZ, Möller E. Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time. Transfusion 1998;38:271–278 [CrossRef][PubMed]
    [Google Scholar]
  91. Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A. Concise review: evidence for CD34 as a common marker for diverse progenitors. Stem Cells 2014;32:1380–1389 [CrossRef][PubMed]
    [Google Scholar]
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