Register      Login
Microbiology Australia Microbiology Australia Society
Microbiology Australia, bringing Microbiologists together
Shopping Cart: ( empty )
You are here: Home > Journals > MA > MA15061
RESEARCH ARTICLE
Contents Vol 36(4)

Cytomegalovirus infection and pathogenesis in the human placenta

Lenore Pereira A B , Takako Tabata A and Matthew Petitt A
+ Author Affiliations
- Author Affiliations

A Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA

B Tel: 415 476 8248
Email: Lenore.Pereira@UCSF.edu

Microbiology Australia 36(4) 171-174 https://doi.org/10.1071/MA15061
Published: 27 October 2015

Abstract

Human cytomegalovirus (HCMV) is the most common cause of congenital viral infection. Affected children can have permanent neurological complications, including hearing loss, visual impairment and mental retardation1–3. In Australia, 57% of women are seronegative and at risk for primary infection and transmission of virus to the fetus during pregnancy4. Despite its public health significance, the specific molecular and cellular basis of HCMV replication in the human placenta and pathogenesis associated with poor clinical outcome are unknown. Direct fetal infection is involved in severe cases of neuropathology and infection of the placenta can impair its development and functions resulting in a hypoxic environment5–8 and stillbirth6,9,10. Gestational age at the time of infection is an important determinant of outcome. The rates of virus transmission increase from 30% in first trimester to over 70% in third trimester suggesting different mechanisms for overcoming the placental barrier2. Remarkable insights into viral pathogenesis factors that function in the tissue environment have been gained by studying congenitally infected placentas and explants infected by clinical strains ex vivo. Together these studies revealed that direct infection of specialised placental cells and paracrine factors contribute to impaired development and functional defects.


References

[1]  Boppana, S.B. et al. (2001) Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N. Engl. J. Med. 344, 1366–1371.
| Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3kvFejtw%3D%3D&md5=035d1440452daca9662e1fd2356783cfCAS | 11333993PubMed |

[2]  Cannon, M.J. and Pellett, P.E. (2005) Risk of congenital cytomegalovirus infection. Clin. Infect. Dis. 40, 1701–1702.
| Risk of congenital cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 15889375PubMed |

[3]  Pass, R.F. et al. (2006) Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J. Clin. Virol. 35, 216–220.
| Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome.Crossref | GoogleScholarGoogle Scholar | 16368262PubMed |

[4]  Basha, J. et al. (2014) Congenital cytomegalovirus infection is associated with high maternal socio-economic status and corresponding low maternal cytomegalovirus seropositivity. J. Paediatr. Child Health 50, 368–372.
| Congenital cytomegalovirus infection is associated with high maternal socio-economic status and corresponding low maternal cytomegalovirus seropositivity.Crossref | GoogleScholarGoogle Scholar | 24593837PubMed |

[5]  Fisher, S. et al. (2000) Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis. J. Virol. 74, 6808–6820.
| Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXkvFCmt78%3D&md5=149f24ac07c6790e8fa3cddeb726b792CAS | 10888620PubMed |

[6]  Gabrielli, L. et al. (2012) Congenital cytomegalovirus infection: patterns of fetal brain damage. Clin. Microbiol. Infect. 18, E419–E427.
| Congenital cytomegalovirus infection: patterns of fetal brain damage.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38fntVKrsw%3D%3D&md5=aaf84d8b7a9e2a36f57b4c23b56b428dCAS | 22882294PubMed |

[7]  Maidji, E. 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, 1298–1310.
| Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1KmsbzK&md5=83e1a5e447e98aeb7988d620a6470c22CAS | 20651234PubMed |

[8]  Pereira, L. et al. (2014) Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection. J. Infect. Dis. 209, 1573–1584.
| Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXnt1CmtLg%3D&md5=fe270b2b7d97aa348ac72318112cd191CAS | 24403553PubMed |

[9]  Pass, R.F. et al. (2009) Vaccine prevention of maternal cytomegalovirus infection. N. Engl. J. Med. 360, 1191–1199.
| Vaccine prevention of maternal cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjtlersbk%3D&md5=37fbcd143155580003a2aef0c548f566CAS | 19297572PubMed |

[10]  Red-Horse, K. et al. (2006) Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation. J. Clin. Invest. 116, 2643–2652.
| Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVKgu7rJ&md5=4509ff83e57bf29877d67dcc99e422c6CAS | 16998586PubMed |

[11]  Fu, T.M. et al. (2014) Progress on pursuit of human cytomegalovirus vaccines for prevention of congenital infection and disease. Vaccine 32, 2525–2533.
| Progress on pursuit of human cytomegalovirus vaccines for prevention of congenital infection and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXlvVWhu78%3D&md5=b62d1a68b008305c36b082988d452b6fCAS | 24681264PubMed |

[12]  McCormick, A.L. and Mocarski, E.S. (2015) The immunological underpinnings of vaccinations to prevent cytomegalovirus disease. Cell. Mol. Immunol. 12, 170–179.
| The immunological underpinnings of vaccinations to prevent cytomegalovirus disease.Crossref | GoogleScholarGoogle Scholar | 25544503PubMed |

[13]  Wang, D. and Fu, T.M. (2014) Progress on human cytomegalovirus vaccines for prevention of congenital infection and disease. Curr. Opin. Virol. 6, 13–23.
| Progress on human cytomegalovirus vaccines for prevention of congenital infection and disease.Crossref | GoogleScholarGoogle Scholar | 24632198PubMed |

[14]  Maltepe, E. et al. (2010) The placenta: transcriptional, epigenetic, and physiological integration during development. J. Clin. Invest. 120, 1016–1025.
| The placenta: transcriptional, epigenetic, and physiological integration during development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksVChs7w%3D&md5=16a22eb92f336f5e837581717badac4eCAS | 20364099PubMed |

[15]  Maidji, E. et al. (2002) Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts. Virology 304, 53–69.
| Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XpsFyhtL0%3D&md5=4ab3b457f601818c6023a716cc0b1f62CAS | 12490403PubMed |

[16]  Pereira, L. et al. (2003) Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity. J. Virol. 77, 13301–13314.
| Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpslSms7s%3D&md5=9da0c4f219eed80b09d8dbf43631e4efCAS | 14645586PubMed |

[17]  Tabata, T. et al. (2007) Cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell–matrix and cell–cell adhesion molecules: a quantitative analysis. Placenta 28, 527–537.
| Cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell–matrix and cell–cell adhesion molecules: a quantitative analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksV2mtrs%3D&md5=f32ac3c429758c0cd4cc4f58c90eb786CAS | 16822542PubMed |

[18]  Tabata, T. et al. (2015) Human cytomegalovirus infection interferes with the maintenance and differentiation of trophoblast progenitor cells of the human placenta. J. Virol. 89, 5134–5147.
| Human cytomegalovirus infection interferes with the maintenance and differentiation of trophoblast progenitor cells of the human placenta.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXntFajs7g%3D&md5=79cc7bf2fa70b76f8039ae8c5828ad50CAS | 25741001PubMed |

[19]  Zydek, M. et al. (2014) HCMV infection of human trophoblast progenitor cells of the placenta is neutralized by a human monoclonal antibody to glycoprotein B and not by antibodies to the pentamer complex. Viruses 6, 1346–1364.
| HCMV infection of human trophoblast progenitor cells of the placenta is neutralized by a human monoclonal antibody to glycoprotein B and not by antibodies to the pentamer complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhs1GrtrrI&md5=b2ed8e118c4c69e770817bc08d1ab9b3CAS | 24651029PubMed |

[20]  Nozawa, N. et al. (2009) Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream. J. Clin. Virol. 46, S58–S63.
| Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVGntLrN&md5=d21c809ec71acc85981940e07caf1295CAS | 19854676PubMed |

[21]  Fournier, T. et al. (2011) PPARgamma and human trophoblast differentiation. J. Reprod. Immunol. 90, 41–49.
| PPARgamma and human trophoblast differentiation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXos1ygsbw%3D&md5=28c5ae872e948e84282251dd2b19e069CAS | 21704384PubMed |

[22]  Kauvar, L.M. et al. (2015) A high affinity native human antibody blocks human cytomegalovirus infection of diverse cell types. Antimicrob. Agents Chemother. , .
| A high affinity native human antibody blocks human cytomegalovirus infection of diverse cell types.Crossref | GoogleScholarGoogle Scholar | 25534746PubMed |

[23]  Tabata, T. et al. (2008) Induction of an epithelial integrin αvβ6 in human cytomegalovirus-infected endothelial cells leads to activation of transforming growth factor-β1 and increased collagen production. Am. J. Pathol. 172, 1127–1140.
| Induction of an epithelial integrin αvβ6 in human cytomegalovirus-infected endothelial cells leads to activation of transforming growth factor-β1 and increased collagen production.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXislOht78%3D&md5=b8dd9f647a464dfc8f79635663ebd1f2CAS | 18349127PubMed |

[24]  Yamamoto-Tabata, T. et al. (2004) Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro. J. Virol. 78, 2831–2840.
| Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXitlSntLw%3D&md5=850d4ca33b8056a499a218eeb39080c4CAS | 14990702PubMed |

[25]  Maidji, E. et al. (2007) Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta. J. Virol. 81, 4701–4712.
| Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXkvFChtr4%3D&md5=68560729cfdb1e491006400ba8292341CAS | 17314173PubMed |

[26]  Maidji, E. et al. (2006) Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis. Am. J. Pathol. 168, 1210–1226.
| Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjslOhtLc%3D&md5=3e52b75b9d1fc1f8551ea9d3b4dbefa4CAS | 16565496PubMed |

[27]  McDonagh, S. et al. (2004) Viral and bacterial pathogens at the maternal-fetal interface. J. Infect. Dis. 190, 826–834.
| Viral and bacterial pathogens at the maternal-fetal interface.Crossref | GoogleScholarGoogle Scholar | 15272412PubMed |

[28]  McDonagh, S. et al. (2006) Patterns of human cytomegalovirus infection in term placentas: a preliminary analysis. J. Clin. Virol. 35, 210–215.
| Patterns of human cytomegalovirus infection in term placentas: a preliminary analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjvVKgsg%3D%3D&md5=f9bf2b4d19f5d0c6fa84e1647f39c483CAS | 16386950PubMed |

[29]  Tabata, T. et al. (2012) Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model. Am. J. Pathol. 181, 1540–1559.
| Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslOltbvM&md5=e7955d7d2c9a1a349ca5359a9d9aed12CAS | 22959908PubMed |

[30]  Co, E.C. et al. (2013) Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy. Biol. Reprod. 88, 155.
| Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy.Crossref | GoogleScholarGoogle Scholar | 23553431PubMed |