{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T17:59:57Z","timestamp":1767203997765,"version":"build-2238731810"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Zika virus (ZIKV) infection has been associated with neurological syndromes, particularly during outbreaks caused by Asian lineage strains. However, experimental models suggest that African strains may exhibit an equal or more virulent profile. Neuroinvasion by systemic viruses often requires crossing the blood\u2013brain barrier (BBB), which disruption amplifies viral dissemination and neuropathology. Type I interferons (IFNs) are key to restricting ZIKV replication, but their specific role in preserving BBB integrity remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we used human brain microvascular endothelial cells (HBMECs) as a simplified BBB model to compare transcriptional responses and IFN modulation following infection with either the African prototype strain ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      or the Asian epidemic strain ZIKV\n                      <jats:sub>PE243<\/jats:sub>\n                      . The role of endothelial cell\u2013mediated IFN responses was further assessed\n                      <jats:italic>in vivo<\/jats:italic>\n                      by intravascular inoculation of mice with endothelial-specific IFNAR depletion using ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      Infection of HBMEC with ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      triggered a greater number and broader range of differentially expressed genes, especially ones associated with interferon signaling and translational pathways, whereas ZIKV\n                      <jats:sub>PE243<\/jats:sub>\n                      -infected samples clustered closer to non-infected ones. ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      infection also resulted in higher viral titers and faster dissemination across endothelial monolayers. Both strains induced IFN-\u03b2 expression but suppressed downstream IFN signaling by reducing STAT1 phosphorylation and promoting STAT2 degradation, with these effects being more pronounced for ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      . 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\n                      <jats:sub>PE243<\/jats:sub>\n                      showing greater sensitivity to IFN-\u03b2. Importantly,\n                      <jats:italic>in vivo<\/jats:italic>\n                      infection of mice lacking endothelial IFNAR signaling resulted in elevated CNS viral load and increased lethality following ZIKV\n                      <jats:sub>MR766<\/jats:sub>\n                      infection, underscoring the pivotal role of endothelial IFN responses in viral control, maintenance of BBB integrity, and protection against neuroinvasion.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1726007","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T06:38:47Z","timestamp":1764743927000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct ZIKV strain signatures and type I IFN modulation reveal a protective role of brain endothelial interferon signaling in vitro and in vivo"],"prefix":"10.3389","volume":"15","author":[{"given":"Luan Rocha","family":"Lima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin Mucun\u00e3","family":"Mustaf\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula Luize Camargos","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharton Vin\u00edcius Antunes","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierina Lorencini","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Lopes","family":"Simeoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana Monteiro","family":"Meuren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Braz","family":"Bezerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathane Cunha","family":"Mebus-Antunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Matassoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Luiz","family":"Proen\u00e7a-Modena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato Santana","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Barros de","family":"Arruda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. 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