{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:55:21Z","timestamp":1787507721856,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005869","name":"Universit\u00e9 de Fribourg","doi-asserted-by":"publisher","award":["Project 819"],"award-info":[{"award-number":["Project 819"]}],"id":[{"id":"10.13039\/501100005869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013788","name":"Facult\u00e9 des Sciences et de M\u00e9decine, Universit\u00e9 de Fribourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013788","id-type":"DOI","asserted-by":"publisher"}]}],"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>The neurotropic virus Japanese encephalitis virus invades the human central nervous system, inducing neuroinflammation and further disruption of the blood-brain barrier. JEV interacts with various cell types of the blood-brain barrier including the endothelial cells. The present work aims to investigate impact of receptor-dependent and independent infection of human microvascular endothelial cells by Japanese encephalitis virus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Receptor-dependent infection was achieved using cell-free virus while receptor-independent infection was by co-culture of microvascular endothelial cells with virus-associated microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      While both receptor-dependent and independent infections of human microvascular endothelial cells led to virus propagation, only receptor-independent infection induced cell death of human microvascular endothelial cells. While the CX\n                      <jats:sub>3<\/jats:sub>\n                      CR1-CX\n                      <jats:sub>3<\/jats:sub>\n                      CL1 axis was inefficient in blocking virus rescue and protecting endothelial cell from cell death, transcriptomics analysis identified Tumour Necrosis Factor-related apoptosis inducing ligand and receptors as potential key player leading to endothelial cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, our findings demonstrate that human microvascular endothelial cells supply virus propagation and Japanese encephalitis virus-associated microglia greatly contribute to endothelial cell death, an important component of the blood brain barrier integrity. Importantly, Tumour Necrosis Factor-related apoptosis inducing ligand and receptors represents a promising therapeutic target preventing microvascular endothelial cell death after neuroinvasion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1580958","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:50:13Z","timestamp":1746172213000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Japanese encephalitis virus-associated human microglia induce cell death of human microvascular endothelial cells in receptor-independent infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Isabelle","family":"Fellay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Blanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Larionov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Schlunke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Filgueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Lannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0069465","article-title":"Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions","volume":"8","author":"Agrawal","year":"2013","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2017.02.012","article-title":"Japanese encephalitis virus disrupts blood-brain barrier and modulates apoptosis proteins in THBMEC cells","volume":"233","author":"Al-Obaidi","year":"2017","journal-title":"Virus Res."},{"key":"B3","doi-asserted-by":"crossref","first-page":"5530","DOI":"10.1111\/febs.15637","article-title":"The multifaceted role of TRAIL signaling in cancer and immunity","volume":"288","author":"Alves","year":"2021","journal-title":"FEBS J."},{"key":"B4","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1080\/21505594.2021.1899674","article-title":"Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage","volume":"12","author":"Ashraf","year":"2021","journal-title":"Virulence."},{"key":"B5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3389\/fmicb.2017.00303","article-title":"MLKL mediated necroptosis accelerates JEV-induced neuroinflammation in mice","volume":"8","author":"Bian","year":"2017","journal-title":"Front. 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