# Trophoblast development and placental susceptibility to cytomegalovirus infection

> **NIH HD R01** · UNIVERSITY OF MINNESOTA · 2026 · $397,077

## Abstract

Abstract.
Human cytomegalovirus (HCMV) is the most common cause of congenital viral infections. HCMV’s ability to
infect the placenta plays a central role in its pathogenesis during pregnancy. Placental infection can be
sufficient to cause adverse pregnancy outcomes and is likely a prerequisite to congenital cytomegalovirus
infection. The placenta is resistant to viral infection in part due to the antiviral activity of trophoblasts. These
fetal-derived cells form the physical barrier that separates maternal and fetal circulation and secrete a variety
of factors, including type III interferon, exosomes, and antimicrobial peptides, that collectively defend the
maternal-fetal interface from infection. However, HCMV can replicate in trophoblasts and may injure the
placenta either by directly infecting and killing trophoblasts or by stimulating an injurious maternal or fetal
immune response. Two preliminary studies have led us to hypothesize that trophoblast differentiation
sensitizes the placenta to infection-associated injury late in gestation. Firstly, we have found that human
trophoblast stem cells (TSCs) can be infected by HCMV but are not permissive to replication. Transcriptome
profiling revealed that, like other embryonic and multipotent stem cells, TSCs constitutively express a subset of
interferon stimulated genes (ISGs). Suspecting that one or more of these factors protect TSCs and their
derivatives from HCMV during early differentiation, we will conduct an unbiased CRISPR/Cas9 screen to
identify HCMV restriction factors in these cells. Follow up studies will use targeted mutagenesis to study how
ISG deletion affects the sensitivity of TSCs, TSC-derived trophoblasts, and trophoblast organoids to infection.
Separately, studies in a guinea pig model of congenital cytomegalovirus infection revealed that maternal
infection after mid-gestation causes a unique pattern of viral infection in the placenta and a transcriptional
response that implicates placental immunop

## Key facts

- **NIH application ID:** 11322105
- **Project number:** 5R01HD109252-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Craig John Bierle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HD
- **Fiscal year:** 2026
- **Award amount:** $397,077
- **Award type:** 5
- **Project period:** 2022-08-09T00:00:00 → 2027-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11322105

## Citation

> US National Institutes of Health, RePORTER application 11322105, Trophoblast development and placental susceptibility to cytomegalovirus infection (5R01HD109252-05). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11322105. Licensed CC0.

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