{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:50:52Z","timestamp":1792651852434,"version":"4.5.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDB29050201"],"award-info":[{"award-number":["XDB29050201"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2022YFC2303502"],"award-info":[{"award-number":["2022YFC2303502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31925025 and 22293033"],"award-info":[{"award-number":["31925025 and 22293033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871014 and 32271459"],"award-info":[{"award-number":["31871014 and 32271459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood\u2013retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011077","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T18:33:54Z","timestamp":1674066834000},"page":"e1011077","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes"],"prefix":"10.1371","volume":"19","author":[{"given":"Jiawang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-En","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-272X","authenticated-orcid":true,"given":"Zongqiang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ppat.1011077.ref001","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1213\/ANE.0000000000000866","article-title":"Ebola 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barrier and the blood-brain barrier.","volume":"11","author":"CF Chiu","year":"2020","journal-title":"Front Microbiol"},{"key":"ppat.1011077.ref043","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.aaa4919","article-title":"Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates","volume":"348","author":"A Marzi","year":"2015","journal-title":"Science"},{"key":"ppat.1011077.ref044","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/78654","article-title":"Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury","volume":"6","author":"ZY Yang","year":"2000","journal-title":"Nat Med"},{"key":"ppat.1011077.ref045","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1016\/j.celrep.2019.01.069","article-title":"Pseudovirus rVSV\u0394G-ZEBOV-GP infects neurons in retina and CNS, causing apoptosis and neurodegeneration in neonatal mice","volume":"26","author":"IL McWilliams","year":"2019","journal-title":"Cell Rep"},{"key":"ppat.1011077.ref046","doi-asserted-by":"crossref","first-page":"e1006397","DOI":"10.1371\/journal.ppat.1006397","article-title":"Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection","volume":"13","author":"M Iampietro","year":"2017","journal-title":"PLOS Pathog"},{"key":"ppat.1011077.ref047","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4014\/jmb.1711.11025","article-title":"VEGF siRNA Delivery by a Cancer-Specific Cell-Penetrating Peptide","volume":"28","author":"YW Lee","year":"2018","journal-title":"J Microbiol Biotechnol"},{"key":"ppat.1011077.ref048","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.7150\/thno.37678","article-title":"Cardio-renal Exosomes in Myocardial Infarction Serum Regulate Proangiogenic Paracrine Signaling in Adipose Mesenchymal Stem Cells.","volume":"10","author":"L Gao","year":"2020","journal-title":"Theranostics"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T18:34:39Z","timestamp":1674066879000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011077"}},"subtitle":[],"editor":[{"given":"Amy L.","family":"Hartman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011077","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}