Work

DUX4-stimulated genes define an antiviral defense program in human placental trophoblasts

Year: 2025

Type: article

Abstract: The placenta combats mother-to-fetus transmission of viruses through the antiviral activities of fetal-derived trophoblasts. Placental trophoblasts employ specialized antiviral strategies to protect against infection while preventing maternal immune rejection of the fetus. However, the full extent of how trophoblasts respond to viral infections is not well understood. To address this, we defined the transcriptional landscape of human trophoblast organoids infected with seven diverse teratogenic viruses. We found that herpesviruses, including HSV-1, HSV-2, and HCMV, did not trigger an IFN response. Instead, they activated the expression of DUX4 and its downstream target genes: DUX4-stimulated genes (DSGs). This program was enriched in trophoblasts and associated with cells containing low HSV-1 gene expression following infection. Screening highly expressed DSGs revealed that many of them exhibited anti-herpesvirus activity, indicating they comprise an alternative antiviral pathway similar to the IFN-stimulated gene response. These findings identify DUX4 as a master regulator of an antiviral program in trophoblasts, specifically targeting a prominent family of teratogenic viruses.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20250448

Authors: Joshua Hatterschide, Liheng Yang, Carolyn B. Coyne

Institutions: Duke University, Duke Medical Center

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development