Human trophoblast stem cells restrict human cytomegalovirus replication

Tyler B Rollman, Zachary W Berkebile, Hiroaki Okae, Vivian J Bardwell, Micah D Gearhart, Craig J Bierle

Research output: Contribution to journalArticlepeer-review

Abstract

Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiatedinto extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimesterplacenta. HCMV was found to non-productively infect TSCs, EVTs, and STBs. Immunofluorescenceassays and flowcytometry experiments further revealed that infected TSCs frequently only express immediate early viral gene products. Similarly, RNA sequencing found that viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts.Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation,and Wingless/Integrated signaling. Thus, while HCMV does not replicate in TSCs, infection may perturb trophoblast differentiationin ways that could interfere with placental function.

Original languageEnglish (US)
Article numbere01935-23
Pages (from-to)e0193523
JournalJournal of virology
Volume98
Issue number4
Early online dateMar 7 2024
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 American Society for Microbiology.

Keywords

  • congenital infections
  • human cytomegalovirus
  • placenta
  • trophoblast
  • trophoblast stem cells

PubMed: MeSH publication types

  • Journal Article

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