Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using real‐time PCR: Correlation of CMV in the vagina and adverse outcome of pregnancy

Tanaka, Kaori; Yamada, Hideto; Minami, Mashiho; Kataoka, Soromon; Numazaki, Kei; Minakami, Hisanori; Tsutsumi, Hiroyuki

doi:10.1002/jmv.20619

Cited by 41 publications

(43 citation statements)

References 21 publications

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“…Despite its public health significance, however, the specific molecular and cellular basis of HCMV's effects on the placenta and fetus and the reasons why clinical outcomes vary are poorly understood. Although direct fetal infection is involved in severe cases of neuropathology, infection of the placenta-with attendant effects on its development and function leading to an hypoxic environment (16)(17)(18)(19)-can result in IUGR and stillbirth (20)(21)(22).…”

mentioning

confidence: 99%

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

Tabata

Petitt

Zydek

et al. 2015

J Virol

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Human cytomegalovirus (HCMV) is a major cause of birth defects that include severe neurological deficits, hearing and vision loss, and intrauterine growth restriction. Viral infection of the placenta leads to development of avascular villi, edema, and hypoxia associated with symptomatic congenital infection. Studies of primary cytotrophoblasts (CTBs) revealed that HCMV infection impedes terminal stages of differentiation and invasion by various molecular mechanisms. We recently discovered that HCMV arrests earlier stages involving development of human trophoblast progenitor cells (TBPCs), which give rise to the mature cell types of chorionic villi-syncytiotrophoblasts on the surfaces of floating villi and invasive CTBs that remodel the uterine vasculature. Here, we show that viral proteins are present in TBPCs of the chorion in cases of symptomatic congenital infection. In vitro studies revealed that HCMV replicates in continuously self-renewing TBPC lines derived from the chorion and alters expression and subcellular localization of proteins required for cell cycle progression, pluripotency, and early differentiation. In addition, treatment with a human monoclonal antibody to HCMV glycoprotein B rescues differentiation capacity, and thus, TBPCs have potential utility for evaluation of the efficacies of novel antiviral antibodies in protecting and restoring placental development. Our results suggest that HCMV replicates in TBPCs in the chorion in vivo, interfering with the earliest steps in the growth of new villi, contributing to virus transmission and impairing compensatory development. In cases of congenital infection, reduced responsiveness of the placenta to hypoxia limits the transport of substances from maternal blood and contributes to fetal growth restriction. IMPORTANCEHuman cytomegalovirus (HCMV) is a leading cause of birth defects in the United States. Congenital infection can result in permanent neurological defects, mental retardation, hearing loss, visual impairment, and pregnancy complications, including intrauterine growth restriction, preterm delivery, and stillbirth. Currently, there is neither a vaccine nor any approved treatment for congenital HCMV infection during gestation. The molecular mechanisms underlying structural deficiencies in the placenta that undermine fetal development are poorly understood. Here we report that HCMV replicates in trophoblast progenitor cells (TBPCs)-precursors of the mature placental cells, syncytiotrophoblasts and cytotrophoblasts, in chorionic villi-in clinical cases of congenital infection. Virus replication in TBPCs in vitro dysregulates key proteins required for self-renewal and differentiation and inhibits normal division and development into mature placental cells. Our findings provide insights into the underlying molecular mechanisms by which HCMV replication interferes with placental maturation and transport functions. H uman cytomegalovirus (HCMV) is the most common cause of congenital viral infection in the UnitedStates. Each year, at least 4...

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mentioning

confidence: 99%

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

Tabata

Petitt

Zydek

et al. 2015

J Virol

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“…Although primary infection in any stage of pregnany presents a risk for intrauterine infection from 30-50% but congenital infection in seropostive mothers is only from 0.2 to 1.5 percent, and that it needs more microbiological and histological confirmation (Stagno, 1990). The results of Tanaka et al, (2006) suggested that latent CMV infection predisposes to adverse pregnancy outcomes (Tanaka et al, 2006).…”

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confidence: 99%

Cytomegalovirus Immunity in Pregnancy in South of Iran

Jahromi¹

2010

American Journal of Infectious Diseases

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Problem statement: Fetal loss and abortion are responsible for significant emotional distress for couples desiring children. There are many documents which support the role of some certain asymptomatic infections such as Cytomegalovirus (CMV) in spontaneous abortion. This study was aimed to evaluate the prevalence of seropositivity for CMV IgG and IgM in women with abortion and compare it with normal women with no previous history of abortion. Approach: This case-control study was carried out in Shariatee hospital of Hormozgan University of medical sciences, during [2003][2004]. A number of 250 women with definite diagnosis of previous abortion and 200 matched women with normal full term delivery and negative history of miscarriage as controls were studied as case and control groups. Serum samples were obtained from participants and a demographic questionnaire was also filled for each of them. .All serum samples were then tested using ELISA method for detection of anti-CMV IgM and IgG Antibodies. Data was analyzed, using SPSS software (chi square and t-test). Results: The average age was 25.6±7.6 years in case group and 25.3±6.5 years in control group. The number and percentage for CMV-IgG was 235(94%) and 150(75%) in case and control groups, respectively (p-value = 0.0001). In case group 13(5.2%) women were positive for CMV-IgM, while no positive sample was detected in control group (p-value = 0.0001). Conclusion: This study showed higher prevalence of seropositivity for CMV in women with spontaneous abortion comparing to women with normal full term delivery and suggest that cytomegalovirus plays a significant role in abortion.

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“…It is known that CMV shedding in the genital secretions may be prolonged after primary infection [15] and could also represent reactivation of latent virus [16]. In addition, it was reported that 7.7% of healthy pregnant women tested positive for CMV-DNA in the vaginal secretion during the first trimester [17]. The percentage of patients with positive CMV-DNA PCR results for the cervical secretion in pregnant women with congenital CMV infection was much higher than that in women without congenital CMV infection or that in healthy pregnant women.…”

Section: Cmv-dna Pcr Test Of Uterine Cervical Secretion May Be a Novementioning

confidence: 99%

PCR tests for uterine cervical secretion are promising noninvasive methods for predicting congenital cytomegalovirus infection

Tanimura

Ebina

Yamada

2017

Expert Review of Molecular Diagnostics

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Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using real‐time PCR: Correlation of CMV in the vagina and adverse outcome of pregnancy

Cited by 41 publications

References 21 publications

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

Cytomegalovirus Immunity in Pregnancy in South of Iran

PCR tests for uterine cervical secretion are promising noninvasive methods for predicting congenital cytomegalovirus infection

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