{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:24:14Z","timestamp":1788269054468,"version":"build-2803163510"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Severe COVID-19 is frequently associated with vascular complications, raising ongoing debate about whether SARS-CoV-2 can directly infect endothelial cells and thereby contribute to disease pathogenesis. Although endothelial cells express angiotensin-converting enzyme 2 (ACE2), the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      relevance of endothelial-restricted viral tropism remains unclear. To directly assess the consequences of endothelial-restricted SARS-CoV-2 tropism\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , we generated a transgenic mouse model expressing human ACE2 under control of the endothelial-specific\n                      <jats:italic toggle=\"yes\">Cdh5<\/jats:italic>\n                      promoter (\n                      <jats:italic toggle=\"yes\">Cdh5<\/jats:italic>\n                      -hACE2). Despite confirmed pulmonary endothelial expression and protein presence of hACE2, SARS-CoV-2 infection of\n                      <jats:italic toggle=\"yes\">Cdh5<\/jats:italic>\n                      -hACE2 mice did not induce clinical illness, detectable viral replication, immune cell influx in the lung, or histopathological abnormalities in the lung or brain. These findings indicate that endothelial-restricted SARS-CoV-2 tropism alone is insufficient to drive productive infection and clinical disease\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , suggesting that endothelial involvement in COVID-19 likely arises in the context of broader cellular infection or systemic host responses rather than from primary endothelial infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Although SARS-CoV-2 primarily infects the upper and lower airways, COVID-19 was quickly recognized as a multi-organ disease, in which vascular complications are a recurring feature. This has raised the possibility that direct infection of endothelial cells contributes to disease pathogenesis. However, whether vascular injury arises from productive endothelial infection or instead represents a secondary consequence of systemic inflammation remains unresolved. To directly disentangle these possibilities and define the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      consequences of endothelial-restricted viral tropism, we generated a transgenic mouse model expressing human ACE2 under the control of the endothelial-specific\n                      <jats:italic toggle=\"yes\">Cdh5<\/jats:italic>\n                      promoter (\n                      <jats:italic toggle=\"yes\">Cdh5<\/jats:italic>\n                      -hACE2).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01311-26","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:00:11Z","timestamp":1786453211000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting endothelial tropism of SARS-CoV-2 using a cell-specific hACE2 mouse model"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3910-3763","authenticated-orcid":true,"given":"Sahine","family":"Lameire","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05wcr1b38","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research","place":["Ghent, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/00cv9y106","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine and Pediatrics, Ghent University","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nincy","family":"Debeuf","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05wcr1b38","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research","place":["Ghent, 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