Human Cytomegalovirus Transmission from the Uterus tothe Placenta Correlates with the Presence of Pathogenic Bacteria andMaternalImmunity

Abstract

Prenatal cytomegalovirus infection may cause pregnancy complications such as intrauterine growth restriction and birth defects. How virus from the mother traverses the placenta is unknown. PCR analysis of biopsy specimens of the maternal-fetal interface revealed that DNA sequences from cytomegalovirus were commonly found with those of herpes simplex viruses and pathogenic bacteria. Cytomegalovirus DNA and infected cell proteins were found more often in the decidua than in the placenta, suggesting that the uterus functions as a reservoir for infection. In women with low neutralizing titers, cytomegalovirus replicated in diverse decidual cells and placental trophoblasts and capillaries. In women with intermediate to high neutralizing titers, decidual infection was suppressed and the placenta was spared. Overall, cytomegalovirus virions and maternal immunoglobulin G were detected in syncytiotrophoblasts, villus core macrophages, and dendritic cells. These results suggest that the outcome of cytomegalovirus infection depends on the presence of other pathogens and coordinated immune responses to viral replication at the maternal-fetal interface.

Risks associated with viral infections during pregnancy

“…They are not expressed on the surface of the syncytiotrophoblast but are expressed on the extravillous trophoblast (15,16). Finger-Jardim et al reported a 9% prevalence of HSV-2 in placental samin endothelial cells, invasive cytotrophoblast, fibroblasts, and the glandular epithelium (7,8), than in the placenta. Decidual infection can occur in the first, second, or third trimester and is affected by variations in local maternal innate immune cells.…”

“…As discussed below, coinfections, or polymicrobial infections, are an important factor in allowing pathogens to damage the syncytial layer, thereby permitting the virus to cross and reach the fetal side. Alternatively, the presence of other pathogens could activate latent CMV in the decidual-immune reservoir (7). Another member of the Herpesviridae family, herpes simplex virus (HSV), is estimated to infect the decidua and/or placenta in 6% to 14% of pregnancies (7,11) and, like CMV, is more likely to be identified in the decidua than in the placenta (7,12).…”

“…Alternatively, the presence of other pathogens could activate latent CMV in the decidual-immune reservoir (7). Another member of the Herpesviridae family, herpes simplex virus (HSV), is estimated to infect the decidua and/or placenta in 6% to 14% of pregnancies (7,11) and, like CMV, is more likely to be identified in the decidua than in the placenta (7,12). Deciduitis and villitis have been described in relation to HSV infections (13), which may explain the association between primary maternal infection with HSV and increased risk of miscarriage and fetal death (14).…”

Cytomegalovirus infection and pathogenesis in the human placenta

“…Our studies of HCMV infection in the human placenta revealed important differences in infection between cell types [15][16][17][18][19] and maternal immune status 7,8,16,20 . Studies of primary human placental cells and tissue models have identified molecular pathways that impair trophoblast differentiation [17][18][19][21][22][23][24] .…”

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

“…There is a relationship between the clinical course of patients with septic shock and acute CMV infection. 44 Pereira et al 45 reported that CMV infection depends on the presence of other pathogens, such as bacteria, and on the coordinated immune response to viral replication in the placenta. LPS is known to signal via Toll-like receptor (TLR)-4, thus having pro-inflammatory properties.…”