Distinct ZIKV strain signatures and type I IFN modulation reveal a protective role of brain endothelial interferon signaling in vitro and in vivo
Infection of HBMEC with ZIKV<sub>MR766</sub> triggered a greater number and broader range of differentially expressed genes, especially ones associated with interferon signaling and translational pathways, whereas ZIKV<sub>PE243</sub>-infected samples clustered closer to non-infected ones. ZIKV<sub>MR766</sub> infection also resulted in higher viral titers and faster dissemination across endothelial monolayers. Both strains induced IFN-β expression but suppressed downstream IFN signaling by reducing STAT1 phosphorylation and promoting STAT2 degradation, with these effects being more pronounced for ZIKV<sub>MR766</sub>. Despite these evasion mechanisms, neutralization assays revealed that endothelial cells-derived IFNs production and response partially restricted viral replication, preserved HBMEC viability, and protected against barrier disruption, with ZIKV<sub>PE243</sub> showing greater sensitivity to IFN-β. Importantly, <i>in vivo</i> infection of mice lacking endothelial IFNAR signaling resulted in elevated CNS viral load and increased lethality following ZIKV<sub>MR766</sub> infection, underscoring the pivotal role of endothelial IFN responses in viral control, maintenance of BBB integrity, and protection against neuroinvasion.
Authors
- Camila L. Simeoni (ORCID: https://orcid.org/0000-0003-2288-5500)
- Renato Santana Aguiar (ORCID: https://orcid.org/0000-0001-5180-3717)
- Lı́dia Moreira Lima (ORCID: https://orcid.org/0000-0002-8625-6351)
- Sharton Vinícius Antunes Coelho (ORCID: https://orcid.org/0000-0003-0794-7160)
- Lana Monteiro Meuren
- Paula Luize Camargos Fonseca (ORCID: https://orcid.org/0000-0002-8103-9235)
- P. Parisi (ORCID: https://orcid.org/0000-0003-2639-2957)
- Bruno Braz Bezerra (ORCID: https://orcid.org/0000-0002-0847-2980)
- Yasmin Mucunã Mustafá
- José Luiz Proença‐Módena (ORCID: https://orcid.org/0000-0002-4996-3153)
- Luciana Barros de Arruda (ORCID: https://orcid.org/0000-0002-7011-7197)
- Flavio Matassoli (ORCID: https://orcid.org/0009-0000-5559-8781)
- Nathane C. Mebus-Antunes (ORCID: https://orcid.org/0000-0002-8973-3635)
Institutions
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal do Rio de Janeiro (BR)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- D’Or Institute for Research and Education (BR)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Frontiers in Cellular and Infection Microbiology
- Published
- 2025-12-03
- DOI
- https://doi.org/10.3389/fcimb.2025.1726007
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministério da Ciência, Tecnologia e Inovação
- Financiadora de Estudos e Projetos
- Universidade Federal do Rio de Janeiro
- Uniformed Services University of the Health Sciences