Spatial Transcriptomic Profiling of the Human Placenta in Congenital Cytomegalovirus Infection: A Broad Antiviral Response with Concurrent Suppression of Trophoblast and Vascular Programs.
5 affiliations
- 1Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- 2Department of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- 3Department of Pathology, Children's Wisconsin, Milwaukee, WI 53226, USA.
- 4Department of Pediatrics, Bioinformatics and Quantitative Child Health, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
- 5Iowa NeuroBank Core, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52246, USA.
Abstract
Congenital cytomegalovirus (CMV) is the most common congenital infection and a leading infectious cause of childhood hearing loss and neurodevelopmental disability. The cellular organization of the placental response to infection is incompletely defined. We applied Visium CytAssist spatial transcriptomics to formalin-fixed tissue from two CMV-infected and two uninfected late-gestation placentas and annotated the major maternal and fetal cell populations by reference-based label transfer. Across 16,074 spatial spots, the only significant compositional changes were increased T cell spots and decreased syncytiotrophoblast-enriched spots in CMV-infected placentas; the remaining populations showed similar changes but did not reach significance. Differential expression comparing CMV-infected to uninfected samples within each cell type identified two opposing programs. Infected placentas displayed a broad interferon-stimulated gene signature accompanied by induction of CXCR3-ligand chemokines, antigen-processing machinery, and the major histocompatibility complex class I transactivator NLRC5, classical-pathway complement components, and lymphocyte and plasma-cell markers, most pronounced in endothelial, stromal, and syncytiotrophoblast clusters and minimal in extravillous trophoblasts. Concurrently, infected placentas showed downregulation of trophoblast differentiation and syncytialization genes, including PAPPA2, pregnancy-specific glycoproteins, CGA, and GCM1, as well as vascular and hemostatic genes, including FLT1, VEGFA, PECAM1, and TFPI2. These data provide a cell-type-resolved molecular correlation of immune activation and placental dysfunction associated with congenital CMV. Together, the data indicate that congenital CMV infection is associated with a coordinated shift at the maternal-fetal interface, in which a broad interferon-driven immune response accompanies suppression of trophoblast-developmental and vascular programs, providing a cell-type-resolved reference for larger studies of placental CMV transmission. Future studies in larger cohorts will be needed to confirm these findings.
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BibTeX
@article{atkinson2026spatial,
title = {{Spatial Transcriptomic Profiling of the Human Placenta in Congenital Cytomegalovirus Infection: A Broad Antiviral Response with Concurrent Suppression of Trophoblast and Vascular Programs.}},
author = {Samantha N Atkinson and Halli E Miller and Jason Jarzembowski and Christine Duris and Amy Y Pan and Li-Chun Lin and Ravit Arav-Boger},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v18101095},
url = {https://europepmc.org/article/MED/42944015},
note = {CC BY},
}
RIS
TY - JOUR
TI - Spatial Transcriptomic Profiling of the Human Placenta in Congenital Cytomegalovirus Infection: A Broad Antiviral Response with Concurrent Suppression of Trophoblast and Vascular Programs.
AU - Samantha N Atkinson
AU - Halli E Miller
AU - Jason Jarzembowski
AU - Christine Duris
AU - Amy Y Pan
AU - Li-Chun Lin
AU - Ravit Arav-Boger
PY - 2026
DA - 2026/10/03
JO - Viruses
DO - 10.3390/v18101095
UR - https://europepmc.org/article/MED/42944015
AB - Congenital cytomegalovirus (CMV) is the most common congenital infection and a leading infectious cause of childhood hearing loss and neurodevelopmental disability. The cellular organization of the placental response to infection is incompletely defined. We applied Visium CytAssist spatial transcriptomics to formalin-fixed tissue from two CMV-infected and two uninfected late-gestation placentas and annotated the major maternal and fetal cell populations by reference-based label transfer. Across 16,074 spatial spots, the only significant compositional changes were increased T cell spots and decreased syncytiotrophoblast-enriched spots in CMV-infected placentas; the remaining populations showed similar changes but did not reach significance. Differential expression comparing CMV-infected to uninfected samples within each cell type identified two opposing programs. Infected placentas displayed a broad interferon-stimulated gene signature accompanied by induction of CXCR3-ligand chemokines, antigen-processing machinery, and the major histocompatibility complex class I transactivator NLRC5, classical-pathway complement components, and lymphocyte and plasma-cell markers, most pronounced in endothelial, stromal, and syncytiotrophoblast clusters and minimal in extravillous trophoblasts. Concurrently, infected placentas showed downregulation of trophoblast differentiation and syncytialization genes, including PAPPA2, pregnancy-specific glycoproteins, CGA, and GCM1, as well as vascular and hemostatic genes, including FLT1, VEGFA, PECAM1, and TFPI2. These data provide a cell-type-resolved molecular correlation of immune activation and placental dysfunction associated with congenital CMV. Together, the data indicate that congenital CMV infection is associated with a coordinated shift at the maternal-fetal interface, in which a broad interferon-driven immune response accompanies suppression of trophoblast-developmental and vascular programs, providing a cell-type-resolved reference for larger studies of placental CMV transmission. Future studies in larger cohorts will be needed to confirm these findings.
SN - 1999-4915
ER -