Persistent human cytomegalovirus infection of the amnion in preterm birth and intrauterine growth restriction

Summary: 
Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of birth defects and preterm birth, and African American and Hispanic women are at four- to five-fold greater risk for infection during reproductive years than white women, contributing to racial disparities in preterm birth. 

Principal Investigators:
Takako Tabata  | Gladstone Institutes | UCSF School of Medicine

Background

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of birth defects and preterm birth, and African American and Hispanic women are at four- to five-fold greater risk for infection during reproductive years than white women, contributing to racial disparities in preterm birth. 

Objective

We discovered that epithelial cells of the amniotic membrane surrounding the fetus develop a persistent infection, producing inflammatory cytokines that can cause preterm labor. 

Method

To prevent preterm birth in congenital HCMV infection, we identified factors that enable persistent infection and demonstrated that interfering with one of these factors –production of the anti-cell death protein survivin – selectively eliminates persistently infected cells.

Results

Using placental organ cultures, we also found that monoclonal antibodies against specific viral proteins that are important for viral entry efficiently blocked viral entry cell-to-cell transmission of virus, and cell death at very low concentrations when compared to currently available antibody preparations, suggesting these specific antibodies could be more effective at protecting against the consequences of congenital HCMV infection, including preterm birth. We also found in a limited study that congenital HCMV infection was present in a large percentage of cases of Zika virus infection associated with microcephaly, suggesting it make act as a cofactor that enhances the risk of other infections.  This work has potential to reduce the risk of preterm birth, especially in communities disproportionately affected by HCMV.

Read the full study

Persistent Cytomegalovirus Infection in Amniotic Membranes of the Human Placenta