{"doi":"10.1101/2025.04.28.651113","title":"Interleukin-27 is antiviral at the maternal-fetal interface","abstract":"ABSTRACT Congenital viral infections can have severe consequences for pregnancy and fetal outcomes. Remarkably, the fetal-derived placenta serves as a robust barrier to infection through meticulous regulation by immune effectors and a diverse repertoire of cytokines. Yet, the regulatory roles of many cytokines remain undefined at the maternal-fetal interface. Interleukin 27 (IL-27) is a highly expressed cytokine in the placenta whose functional consequence during congenital infection is unknown. Here, we utilized trophoblast organoids (TO) derived from primary human placentas and a mouse model of congenital viral infection to uncover the functional role of IL-27 signaling during pregnancy. We show that TOs constitutively express IL-27 and its receptor, IL27RA, and demonstrate that IL-27 signaling restricts Zika virus (ZIKV) infection of TOs. Through bulk RNA-sequencing of TOs in the absence and presence of IL-27 signaling, we demonstrate IL-27-mediated upregulation of antiviral genes. Finally, we show that IL-27 signaling is critical within the context of congenital murine ZIKV infection, as IL-27 restricts placental ZIKV burdens and protects against pathologic fetal outcomes early in gestation. These findings collectively demonstrate a novel role for IL-27 in the placenta and establish IL-27 as an innate antiviral defense at the maternal-fetal interface during congenital viral infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565088,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1443761,"name":"Briah Barksdale","orcid":"0000-0001-9792-2148","position":1,"is_corresponding":false},{"id":576207,"name":"Seble G. Negatu","orcid":"0000-0002-6195-0312","position":2,"is_corresponding":false},{"id":991786,"name":"Rebecca L. Clements","orcid":"0000-0001-9726-1554","position":3,"is_corresponding":false},{"id":321866,"name":"Taylor Miller-Ensminger","orcid":null,"position":4,"is_corresponding":false},{"id":976657,"name":"Alexandra H. Lopez","orcid":"0000-0001-9022-4064","position":5,"is_corresponding":false},{"id":389166,"name":"Sneha Mani","orcid":"0000-0002-5784-041X","position":6,"is_corresponding":false},{"id":389168,"name":"Monica Mainigi","orcid":"0000-0003-3306-4791","position":7,"is_corresponding":false},{"id":305888,"name":"Christopher A. Hunter","orcid":"0000-0003-3092-1428","position":8,"is_corresponding":false},{"id":374670,"name":"Kellie A. Jurado","orcid":"0000-0003-0466-2696","position":9,"is_corresponding":false},{"id":480440,"name":"Madeline S. Merlino","orcid":"0000-0003-2683-3193","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:56:24.872312Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}