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Published in:

01-11-2014 | Review

Models of vertical cytomegalovirus (CMV) transmission and pathogenesis

Authors: Yiska Weisblum, Amos Panet, Ronit Haimov-Kochman, Dana G. Wolf

Published in: Seminars in Immunopathology | Issue 6/2014

Abstract

Despite the considerable clinical impact of congenital human cytomegalovirus (HCMV) infection, the mechanisms of maternal–fetal transmission and the resultant placental and fetal damage are largely unknown. Here, we discuss animal models for the evaluation of CMV vaccines and virus-induced pathology and particularly explore surrogate human models for HCMV transmission and pathogenesis in the maternal–fetal interface. Studies in floating and anchoring placental villi and more recently, ex vivo modeling of HCMV infection in integral human decidual tissues, provide unique insights into patterns of viral tropism, spread, and injury, defining the outcome of congenital infection, and the effect of potential antiviral interventions.

Dollard SC, Grosse SD, Ross DS (2007) New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 17:355–363PubMed

Kenneson A, Cannon MJ (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 17:253–276PubMed

Kern ER (2006) Pivotal role of animal models in the development of new therapies for cytomegalovirus infections. Antiviral Res 71:164–171PubMed

Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK (2013) The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 26:86–102PubMedPubMedCentral

Nelson CT, Demmler GJ (1997) Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant. Clin Perinatol 24:151–160PubMed

Stagno S, Cloud G, Pass RF, Britt WJ, Alford CA (1984) Factors associated with primary cytomegalovirus infection during pregnancy. J Med Virol 13:347–353PubMed

Cannon MJ, Davis KF (2005) Washing our hands of the congenital cytomegalovirus disease epidemic. BMC Public Health 5:70PubMedPubMedCentral

Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD et al (2005) Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 146:817–823PubMed

Fowler KB, Boppana SB (2006) Congenital cytomegalovirus (CMV) infection and hearing deficit. J Clin Virol 35:226–231PubMed

10.

Longo S, Borghesi A, Tzialla C, Stronati M (2014) IUGR and infections. Early Hum Dev 90(Suppl 1):S42–S44PubMed

11.

Pereira L, Petitt M, Fong A, Tsuge M, Tabata T, Fang-Hoover J et al (2014) Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection. J Infect Dis 209:1573–1584PubMed

12.

Daiminger A, Bader U, Enders G (2005) Pre- and periconceptional primary cytomegalovirus infection: risk of vertical transmission and congenital disease. BJOG 112:166–172PubMed

13.

Enders G, Daiminger A, Bader U, Exler S, Enders M (2011) Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 52:244–246PubMed

14.

Liesnard C, Donner C, Brancart F, Gosselin F, Delforge ML, Rodesch F (2000) Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk. Obstet Gynecol 95:881–888PubMed

15.

Pass RF, Fowler KB, Boppana SB, Britt WJ, Stagno S (2006) Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 35:216–220PubMed

16.

Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD et al (1986) Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 256:1904–1908PubMed

17.

Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R (2004) National Vaccine Advisory C. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 39:233–239PubMed

18.

Mocarski ES, Shenk T, Pass RF (2007) Cytomegaloviruses. In: Knipe DM, Howly PM, Griffin DE, Lamb RA, Martin MA (eds) Fields virology, 5th edn. Lippincott Williams and Wilkins, Philadelphia

19.

Enders AC (1965) A comparative study of the fine structure of the trophoblast in several hemochorial placentas. Am J Anat 116:29–67PubMed

20.

Maltepe E, Bakardjiev AI, Fisher SJ (2010) The placenta: transcriptional, epigenetic, and physiological integration during development. J Clin Invest 120:1016–1025PubMedPubMedCentral

21.

McGregor A, Choi KY (2011) Cytomegalovirus antivirals and development of improved animal models. Expert Opin Drug Metab Toxicol 7:1245–1265PubMed

22.

Schlub TE, Sun JC, Walton SM, Robbins SH, Pinto AK, Munks MW et al (2011) Comparing the kinetics of NK cells, CD4, and CD8 T cells in murine cytomegalovirus infection. J Immunol 187:1385–1392PubMedPubMedCentral

23.

Mutnal MB, Cheeran MC, Hu S, Lokensgard JR (2011) Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain. PLoS One 6:e16211PubMedPubMedCentral

24.

Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457:557–561PubMedPubMedCentral

25.

Slavuljica I, Kvestak D, Csaba Huszthy P, Kosmac K, Britt WJ, Jonjic S (2014) Immunobiology of congenital cytomegalovirus infection of the central nervous system-the murine cytomegalovirus model. Cell Mol Immunol. doi:10.1038/cmi.2014.51

26.

Cekinovic D, Golemac M, Pugel EP, Tomac J, Cicin-Sain L, Slavuljica I et al (2008) Passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice. J Virol 82:12172–12180PubMedPubMedCentral

27.

Kumar ML, Nankervis GA (1978) Experimental congenital infection with cytomegalovirus: a guinea pig model. J Infect Dis 138:650–654PubMed

28.

Schleiss MR (2008) Comparison of vaccine strategies against congenital CMV infection in the guinea pig model. J Clin Virol 41:224–230PubMed

29.

Schleiss MR, McVoy MA (2010) Guinea pig cytomegalovirus (GPCMV): a model for the study of the prevention and treatment of maternal-fetal transmission. Futur Virol 5:207–217

30.

Woolf NK, Koehrn FJ, Harris JP, Richman DD (1989) Congenital cytomegalovirus labyrinthitis and sensorineural hearing loss in guinea pigs. J Infect Dis 160:929–937PubMed

31.

Weisblum Y, Panet A, Zakay-Rones Z, Haimov-Kochman R, Goldman-Wohl D, Ariel I et al (2011) Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture. J Virol 85:13204–13213PubMedPubMedCentral

32.

Cross JC, Werb Z, Fisher SJ (1994) Implantation and the placenta: key pieces of the development puzzle. Science 266:1508–1518PubMed

33.

Hamilton WJ, Boyd JD (1960) Development of the human placenta in the first three months of gestation. J Anat 94:297–328PubMedPubMedCentral

34.

Rossant J, Cross JC (2001) Placental development: lessons from mouse mutants. Nat Rev Genet 2:538–548PubMed

35.

Adler SP, Nigro G, Pereira L (2007) Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol 31:10–18PubMed

36.

Knofler M (2010) Critical growth factors and signalling pathways controlling human trophoblast invasion. Int J Dev Biol 54:269–280PubMedPubMedCentral

37.

Pereira L, Maidji E, McDonagh S, Tabata T (2005) Insights into viral transmission at the uterine-placental interface. Trends Microbiol 13:164–174PubMed

38.

Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M et al (2004) Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest 114:744–754PubMedPubMedCentral

39.

Lyall F, Robson SC, Bulmer JN (2013) Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 62:1046–1054PubMed

40.

Zhou Y, Gormley MJ, Hunkapiller NM, Kapidzic M, Stolyarov Y, Feng V et al (2013) Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia. J Clin Invest 123:2862–2872PubMedPubMedCentral

41.

Burton GJ, Jauniaux E, Charnock-Jones DS (2010) The influence of the intrauterine environment on human placental development. Int J Dev Biol 54:303–312PubMed

42.

Hustin J, Gillerot Y, Collette J, Franchimont P (1990) Placental alkaline phosphatase in developing normal and abnormal gonads and in germ-cell tumours. Virchows Arch A Pathol Anat Histopathol 417:67–72PubMed

43.

Jauniaux E, Van Oppenraaij RH, Burton GJ (2010) Obstetric outcome after early placental complications. Curr Opin Obstet Gynecol 22:452–457PubMed

44.

John R, Hemberger M (2012) A placenta for life. Reprod Biomed Online 25:5–11PubMed

45.

Norwitz ER (2006) Defective implantation and placentation: laying the blueprint for pregnancy complications. Reprod Biomed Online 13:591–599PubMed

46.

Pijnenborg R, Anthony J, Davey DA, Rees A, Tiltman A, Vercruysse L et al (1991) Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 98:648–655PubMed

47.

Pijnenborg R, Ball E, Bulmer JN, Hanssens M, Robson SC, Vercruysse L (2006) In vivo analysis of trophoblast cell invasion in the human. Methods Mol Med 122:11–44PubMed

48.

Arck PC, Hecher K (2013) Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat Med 19:548–556PubMed

49.

Erlebacher A (2013) Immunology of the maternal-fetal interface. Annu Rev Immunol 31:387–411PubMed

50.

Mor G, Cardenas I (2010) The immune system in pregnancy: a unique complexity. Am J Reprod Immunol 63:425–433PubMedPubMedCentral

51.

Zenclussen AC (2013) Adaptive immune responses during pregnancy. Am J Reprod Immunol 69:291–303PubMed

52.

Mouillet JF, Ouyang Y, Bayer A, Coyne CB, Sadovsky Y (2014) The role of trophoblastic microRNAs in placental viral infection. Int J Dev Biol 58:281–289PubMed

53.

Zeldovich VB, Bakardjiev AI (2012) Host defense and tolerance: unique challenges in the placenta. PLoS Pathog 8:e1002804PubMedPubMedCentral

54.

Bainbridge DR (2000) Evolution of mammalian pregnancy in the presence of the maternal immune system. Rev Reprod 5:67–74PubMed

55.

Ishitani A, Sageshima N, Lee N, Dorofeeva N, Hatake K, Marquardt H et al (2003) Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. J Immunol 171:1376–1384PubMed

56.

Rapacz-Leonard A, Dabrowska M, Janowski T (2014) Major histocompatibility complex I mediates immunological tolerance of the trophoblast during pregnancy and may mediate rejection during parturition. Mediat Inflamm 2014:579279

57.

Bulmer JN, Pace D, Ritson A (1988) Immunoregulatory cells in human decidua: morphology, immunohistochemistry and function. Reprod Nutr Dev 28:1599–1613PubMed

58.

King A, Loke YW, Chaouat G (1997) NK cells and reproduction. Immunol Today 18:64–66PubMed

59.

Mor G, Straszewski-Chavez SL, Abrahams VM (2006) Macrophage-trophoblast interactions. Methods Mol Med 122:149–163PubMed

60.

Wicherek L, Basta P, Pitynski K, Marianowski P, Kijowski J, Wiatr J et al (2009) The characterization of the subpopulation of suppressive B7H4(+) macrophages and the subpopulation of CD25(+) CD4(+) and FOXP3(+) regulatory T-cells in decidua during the secretory cycle phase, Arias Stella reaction, and spontaneous abortion - a preliminary report. Am J Reprod Immunol 61:303–312PubMed

61.

Manaster I, Mandelboim O (2010) The unique properties of uterine NK cells. Am J Reprod Immunol 63:434–444PubMed

62.

Hunt JS (2006) Stranger in a strange land. Immunol Rev 213:36–47PubMedPubMedCentral

63.

Red-Horse K, Drake PM, Fisher SJ (2004) Human pregnancy: the role of chemokine networks at the fetal-maternal interface. Expert Rev Mol Med 6:1–14PubMed

64.

Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A (2012) Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science 336:1317–1321PubMedPubMedCentral

65.

Redman CW, Sargent IL (2010) Immunology of pre-eclampsia. Am J Reprod Immunol 63:534–543PubMed

66.

Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C, Natanson-Yaron S et al (2006) Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 12:1065–1074PubMed

67.

Hanna J, Mandelboim O (2007) When killers become helpers. Trends Immunol 28:201–206PubMed

68.

Kalkunte S, Chichester CO, Gotsch F, Sentman CL, Romero R, Sharma S (2008) Evolution of non-cytotoxic uterine natural killer cells. Am J Reprod Immunol 59:425–432PubMedPubMedCentral

69.

Moffett-King A (2002) Natural killer cells and pregnancy. Nat Rev Immunol 2:656–663PubMed

70.

Hiby SE, Walker JJ, O’Shaughnessy KM, Redman CW, Carrington M, Trowsdale J et al (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200:957–965PubMedPubMedCentral

71.

Mor G, Romero R, Aldo PB, Abrahams VM (2005) Is the trophoblast an immune regulator? The role of Toll-like receptors during pregnancy. Crit Rev Immunol 25:375–388PubMed

72.

Barry PA, Lockridge KM, Salamat S, Tinling SP, Yue Y, Zhou SS et al (2006) Nonhuman primate models of intrauterine cytomegalovirus infection. ILAR J/Natl Res Counc Inst Lab Anim Res 47:49–64

73.

Schleiss MR (2002) Animal models of congenital cytomegalovirus infection: an overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV). J Clin Virol 25(Suppl 2):S37–S49PubMed

74.

Schleiss MR (2006) Nonprimate models of congenital cytomegalovirus (CMV) infection: gaining insight into pathogenesis and prevention of disease in newborns. ILAR J/Natl Res Counc Inst Lab Anim Res 47:65–72

75.

Wynn KK, Khanna R (2006) Models of CMV infection. Drug Discov Today: Dis Models 3:91–96

76.

Forbes CA, Brown MG, Cho R, Shellam GR, Yokoyama WM, Scalzo AA (1997) The Cmv1 host resistance locus is closely linked to the Ly49 multigene family within the natural killer cell gene complex on mouse chromosome 6. Genomics 41:406–413PubMed

77.

Rodriguez M, Sabastian P, Clark P, Brown MG (2004) Cmv1-independent antiviral role of NK cells revealed in murine cytomegalovirus-infected New Zealand White mice. J Immunol 173:6312–6318PubMed

78.

Scalzo AA, Fitzgerald NA, Simmons A, La Vista AB, Shellam GR (1990) Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen. J Exp Med 171:1469–1483PubMed

79.

Johnson KP (1969) Mouse cytomegalovirus: placental infection. J Infect Dis 120:445–450PubMed

80.

Li RY, Tsutsui Y (2000) Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus. Teratology 62:79–85PubMed

81.

Kawasaki H, Kosugi I, Arai Y, Tsutsui Y (2002) The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection. Lab Invest 82:1347–1358PubMed

82.

Cheeran MC, Lokensgard JR, Schleiss MR (2009) Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev 22:99–126, Table of ContentsPubMedPubMedCentral

83.

Kosugi I, Shinmura Y, Kawasaki H, Arai Y, Li RY, Baba S et al (2000) Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus. Lab Invest 80:1373–1383PubMed

84.

Bantug GR, Cekinovic D, Bradford R, Koontz T, Jonjic S, Britt WJ (2008) CD8+ T lymphocytes control murine cytomegalovirus replication in the central nervous system of newborn animals. J Immunol 181:2111–2123PubMedPubMedCentral

85.

Schachtele SJ, Mutnal MB, Schleiss MR, Lokensgard JR (2011) Cytomegalovirus-induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice. J Neurovirol 17:201–211PubMedPubMedCentral

86.

Kosmac K, Bantug GR, Pugel EP, Cekinovic D, Jonjic S, Britt WJ (2013) Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development. PLoS Pathog 9:e1003200PubMedPubMedCentral

87.

Gabrielli L, Bonasoni MP, Lazzarotto T, Lega S, Santini D, Foschini MP et al (2009) Histological findings in foetuses congenitally infected by cytomegalovirus. J Clin Virol 46(Suppl 4):S16–S21PubMed

88.

Griffith BP, McCormick SR, Fong CK, Lavallee JT, Lucia HL, Goff E (1985) The placenta as a site of cytomegalovirus infection in guinea pigs. J Virol 55:402–409PubMedPubMedCentral

89.

Bia FJ, Griffith BP, Fong CK, Hsiung GD (1983) Cytomegaloviral infections in the guinea pig: experimental models for human disease. Rev Infect Dis 5:177–195PubMed

90.

Choi YC, Hsiung GD (1978) Cytomegalovirus infection in guinea pigs. II. Transplacental and horizontal transmission. J Infect Dis 138:197–202PubMed

91.

Johnson KP, Connor WS (1979) Guinea pig cytomegalovirus: transplacental transmission. Brief report. Arch Virol 59:263–267PubMed

92.

Griffith BP, Lucia HL, Hsiung GD (1982) Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs. Pediatr Res 16:455–459PubMed

93.

Katano H, Sato Y, Tsutsui Y, Sata T, Maeda A, Nozawa N et al (2007) Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model. Microbes Infect 9:183–191PubMed

94.

Schraff SA, Schleiss MR, Brown DK, Meinzen-Derr J, Choi KY, Greinwald JH et al (2007) Macrophage inflammatory proteins in cytomegalovirus-related inner ear injury. Otolaryngol Head Neck Surg 137:612–618PubMed

95.

Leviton MP, Lacayo JC, Choi KY, Hernandez-Alvarado N, Wey A, Schleiss MR (2013) An attenuated cytomegalovirus vaccine with a deletion of a viral chemokine gene is protective against congenital CMV transmission in a guinea pig model. Clin Dev Immunol 2013:906948PubMedPubMedCentral

96.

McDonagh S, Maidji E, Ma W, Chang HT, Fisher S, Pereira L (2004) Viral and bacterial pathogens at the maternal-fetal interface. J Infect Dis 190:826–834PubMed

97.

Revello MG, Gerna G (2004) Pathogenesis and prenatal diagnosis of human cytomegalovirus infection. J Clin Virol 29:71–83PubMed

98.

Trincado DE, Munro SC, Camaris C, Rawlinson WD (2005) Highly sensitive detection and localization of maternally acquired human cytomegalovirus in placental tissue by in situ polymerase chain reaction. J Infect Dis 192:650–657PubMed

99.

Mostoufi-zadeh M, Driscoll SG, Biano SA, Kundsin RB (1984) Placental evidence of cytomegalovirus infection of the fetus and neonate. Arch Pathol Lab Med 108:403–406PubMed

100.

Muhlemann K, Miller RK, Metlay L, Menegus MA (1992) Cytomegalovirus infection of the human placenta: an immunocytochemical study. Hum Pathol 23:1234–1237PubMed

101.

Fisher S, Genbacev O, Maidji E, Pereira L (2000) Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis. J Virol 74:6808–6820PubMedPubMedCentral

102.

Kumazaki K, Ozono K, Yahara T, Wada Y, Suehara N, Takeuchi M et al (2002) Detection of cytomegalovirus DNA in human placenta. J Med Virol 68:363–369PubMed

103.

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 Archiv A Pathol Anat Histopathol 423:249–256

104.

Adler SP, Nigro G (2009) Findings and conclusions from CMV hyperimmune globulin treatment trials. J Clin Virol 46(Suppl 4):S54–S57PubMed

105.

Schleiss MR, Aronow BJ, Handwerger S (2007) Cytomegalovirus infection of human syncytiotrophoblast cells strongly interferes with expression of genes involved in placental differentiation and tissue integrity. Pediatr Res 61:565–571PubMed

106.

Schleiss MR (2006) The role of the placenta in the pathogenesis of congenital cytomegalovirus infection: is the benefit of cytomegalovirus immune globulin for the newborn mediated through improved placental health and function? Clin Infect Dis 43:1001–1003PubMed

107.

Gabrielli L, Bonasoni MP, Santini D, Piccirilli G, Chiereghin A, Petrisli E et al (2012) Congenital cytomegalovirus infection: patterns of fetal brain damage. Clin Microbiol Infect 18:E419–E427PubMed

108.

Garcia AG, Fonseca EF, Marques RL, Lobato YY (1989) Placental morphology in cytomegalovirus infection. Placenta 10:1–18PubMed

109.

Maidji E, Nigro G, Tabata T, McDonagh S, Nozawa N, Shiboski S et al (2010) Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection. Am J Pathol 177:1298–1310PubMedPubMedCentral

110.

Hamilton ST, Scott G, Naing Z, Iwasenko J, Hall B, Graf N et al (2012) Human cytomegalovirus-induces cytokine changes in the placenta with implications for adverse pregnancy outcomes. PLoS One 7:e52899PubMedPubMedCentral

111.

Pereira L, Maidji E, McDonagh S, Genbacev O, Fisher S (2003) Human Cytomegalovirus Transmission from the Uterus to the Placenta Correlates with the Presence of Pathogenic Bacteria and Maternal Immunity. J Virol 77:13301–13314PubMedPubMedCentral

112.

La Torre R, Nigro G, Mazzocco M, Best AM, Adler SP (2006) Placental enlargement in women with primary maternal cytomegalovirus infection is associated with fetal and neonatal disease. Clin Infect Dis 43:994–1000PubMed

113.

Halwachs-Baumann G, Wilders-Truschnig M, Desoye G, Hahn T, Kiesel L, Klingel K et al (1998) Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus. J Virol 72:7598–7602PubMedPubMedCentral

114.

Hemmings DG, Kilani R, Nykiforuk C, Preiksaitis J, Guilbert LJ (1998) Permissive cytomegalovirus infection of primary villous term and first trimester trophoblasts. J Virol 72:4970–4979PubMedPubMedCentral

115.

Maidji E, Percivalle E, Gerna G, Fisher S, Pereira L (2002) Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts. Virology 304:53–69PubMed

116.

Halwachs-Baumann G, Weihrauch G, Gruber HJ, Desoye G, Sinzger C (2006) hCMV induced IL-6 release in trophoblast and trophoblast like cells. J Clin Virol 37:91–97PubMed

117.

Hemmings DG, Guilbert LJ (2002) Polarized release of human cytomegalovirus from placental trophoblasts. J Virol 76:6710–6717PubMedPubMedCentral

118.

Gabrielli L, Losi L, Varani S, Lazzarotto T, Eusebi V, Landini MP (2001) Complete replication of human cytomegalovirus in explants of first trimester human placenta. J Med Virol 64:499–504PubMed

119.

Maidji E, Genbacev O, Chang HT, Pereira L (2007) Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta. J Virol 81:4701–4712PubMedPubMedCentral

120.

Maidji E, McDonagh S, Genbacev O, Tabata T, Pereira L (2006) Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis. Am J Pathol 168:1210–1226PubMedPubMedCentral

121.

Yamamoto-Tabata T, McDonagh S, Chang HT, Fisher S, Pereira L (2004) Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro. J Virol 78:2831–2840PubMedPubMedCentral

122.

LaMarca HL, Nelson AB, Scandurro AB, Whitley GS, Morris CA (2006) Human cytomegalovirus-induced inhibition of cytotrophoblast invasion in a first trimester extravillous cytotrophoblast cell line. Placenta 27:137–147PubMed

123.

Tao L, Suhua C, Juanjuan C, Zongzhi Y, Juan X, Dandan Z (2011) In vitro study on human cytomegalovirus affecting early pregnancy villous EVT’s invasion function. Virol J 8:114PubMedPubMedCentral

124.

Warner JA, Zwezdaryk KJ, Day B, Sullivan DE, Pridjian G, Morris CA (2012) Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion of human extravillous cytotrophoblasts. Virol J 9:255PubMedPubMedCentral

125.

Pereira L, Petitt M, Tabata T (2013) Cytomegalovirus infection and antibody protection of the developing placenta. Clin Inf Dis 57(Suppl 4):S174–S177

126.

Tabata T, Kawakatsu H, Maidji E, Sakai T, Sakai K, Fang-Hoover J et al (2008) Induction of an epithelial integrin alphavbeta6 in human cytomegalovirus-infected endothelial cells leads to activation of transforming growth factor-beta1 and increased collagen production. Am J Pathol 172:1127–1140PubMedPubMedCentral

127.

Tabata T, McDonagh S, Kawakatsu H, Pereira L (2007) Cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell-matrix and cell-cell adhesion molecules: a quantitative analysis. Placenta 28:527–537PubMed

128.

Tabata T, Petitt M, Fang-Hoover J, Rivera J, Nozawa N, Shiboski S et al (2012) Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model. Am J Pathol 181:1540–1559PubMedPubMedCentral

129.

Angelova M, Zwezdaryk K, Ferris M, Shan B, Morris CA, Sullivan DE (2012) Human cytomegalovirus infection dysregulates the canonical Wnt/beta-catenin signaling pathway. PLoS Pathog 8:e1002959PubMedPubMedCentral

130.

Rauwel B, Mariame B, Martin H, Nielsen R, Allart S, Pipy B et al (2010) Activation of peroxisome proliferator-activated receptor gamma by human cytomegalovirus for de novo replication impairs migration and invasiveness of cytotrophoblasts from early placentas. J Virol 84:2946–2954PubMedPubMedCentral

131.

Chan G, Guilbert LJ (2006) Ultraviolet-inactivated human cytomegalovirus induces placental syncytiotrophoblast apoptosis in a Toll-like receptor-2 and tumour necrosis factor-alpha dependent manner. J Pathol 210:111–120PubMed

132.

Chaudhuri S, Lowen B, Chan G, Davey A, Riddell M, Guilbert LJ (2009) Human cytomegalovirus interacts with toll-like receptor 2 and CD14 on syncytiotrophoblasts to stimulate expression of TNFalpha mRNA and apoptosis. Placenta 30:994–1001PubMed

133.

Chan G, Hemmings DG, Yurochko AD, Guilbert LJ (2002) Human cytomegalovirus-caused damage to placental trophoblasts mediated by immediate-early gene-induced tumor necrosis factor-alpha. Am J Pathol 161:1371–1381PubMedPubMedCentral

134.

Schust DJ, Tortorella D, Seebach J, Phan C, Ploegh HL (1998) Trophoblast class I major histocompatibility complex (MHC) products are resistant to rapid degradation imposed by the human cytomegalovirus (HCMV) gene products US2 and US11. J Exp Med 188:497–503PubMedPubMedCentral

135.

Siewiera J, El Costa H, Tabiasco J, Berrebi A, Cartron G, Le Bouteiller P et al (2013) Human cytomegalovirus infection elicits new decidual natural killer cell effector functions. PLoS Pathog 9:e1003257PubMedPubMedCentral

136.

Terauchi M, Koi H, Hayano C, Toyama-Sorimachi N, Karasuyama H, Yamanashi Y et al (2003) Placental extravillous cytotrophoblasts persistently express class I major histocompatibility complex molecules after human cytomegalovirus infection. J Virol 77:8187–8195PubMedPubMedCentral

137.

Jun Y, Kim E, Jin M, Sung HC, Han H, Geraghty DE et al (2000) Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules. J Immunol 164:805–811PubMed

138.

Park B, Spooner E, Houser BL, Strominger JL, Ploegh HL (2010) The HCMV membrane glycoprotein US10 selectively targets HLA-G for degradation. J Exp Med 207:2033–2041PubMedPubMedCentral

139.

Jarvis MA, Nelson JA (2007) Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. J Virol 81:2095–2101PubMedPubMedCentral

140.

Sinzger C, Digel M, Jahn G (2008) Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 325:63–83PubMed

141.

Pereira L, Maidji E (2008) Cytomegalovirus infection in the human placenta: maternal immunity and developmentally regulated receptors on trophoblasts converge. Curr Top Microbiol Immunol 325:383–395PubMed

142.

Compton T, Nepomuceno RR, Nowlin DM (1992) Human cytomegalovirus penetrates host cells by pH-independent fusion at the cell surface. Virology 191:387–395PubMed

143.

Gerna G, Percivalle E, Lilleri D, Lozza L, Fornara C, Hahn G et al (2005) Dendritic-cell 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 86:275–284PubMed

144.

Hahn G, Revello MG, Patrone M, Percivalle E, Campanini G, Sarasini A et al (2004) Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78:10023–10033PubMedPubMedCentral

145.

Ryckman BJ, Jarvis MA, Drummond DD, Nelson JA, Johnson DC (2006) Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 80:710–722PubMedPubMedCentral

146.

Wang D, Shenk T (2005) Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 102:18153–18158PubMedPubMedCentral

147.

Nigro G, Adler SP, La Torre R, Best AM, Congenital Cytomegalovirus Collaborating Group (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353:1350–1362PubMed

148.

Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A et al (2014) A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 370:1316–1326PubMed

Title: Models of vertical cytomegalovirus (CMV) transmission and pathogenesis
Authors: Yiska Weisblum
Amos Panet
Ronit Haimov-Kochman
Dana G. Wolf
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 6/2014
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-014-0449-1

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Models of vertical cytomegalovirus (CMV) transmission and pathogenesis

Abstract

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Abstract

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