Human Trophoblast Stem Cells Restrict Human Cytomegalovirus Replication.

Area of Science:

• Reproductive biology
• Virology
• Stem cell biology

Background:

• Congenital human cytomegalovirus (HCMV) infection, a leading cause of fetal growth restriction and pregnancy loss, originates from placental infection.
• Understanding HCMV's impact on placental development is hindered by species-specificity and limited primary trophoblast models.

Approach:

• Human trophoblast stem cells (TSCs) were utilized as a model to study HCMV infection in the first-trimester placenta.
• HCMV infection dynamics, viral gene expression, and host antiviral responses were assessed in TSCs and their differentiated progeny (EVTs, STBs).

Key Points:

• HCMV establishes non-productive infections in TSCs, EVTs, and STBs, with predominantly immediate early viral gene expression.
• Viral gene expression kinetics in TSCs deviate from typical lytic infection patterns observed in fibroblasts.
• Infected TSCs and trophoblasts show suppressed canonical antiviral responses but dysregulated WNT signaling and factors crucial for cell identity and differentiation.

Conclusions:

• TSCs serve as a valuable model for studying early placental HCMV infection, revealing restricted viral replication.
• HCMV infection in TSCs perturbs trophoblast differentiation and cell fate, offering a potential mechanism for HCMV-induced placental dysfunction and injury.
• Further research into HCMV's effects on trophoblast development is crucial for understanding and mitigating congenital infection consequences.