{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:33:08Z","timestamp":1790213588149,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32503014"],"award-info":[{"award-number":["32503014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"joint research foundation of gansu province","award":["24JRRA804"],"award-info":[{"award-number":["24JRRA804"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The alphaherpesvirus\n                      <jats:italic toggle=\"yes\">Pseudorabies virus<\/jats:italic>\n                      (PRV), which causes Aujeszky\u2019s disease (AD), primarily infects swine but has zoonotic potential and can infect multiple species, including humans. Upon infection, interferons (IFNs) trigger the expression of hundreds of interferon-stimulated genes (ISGs), thereby establishing a robust cellular antiviral state. However, ISGs exhibiting anti-alphaherpesvirus activity have not yet been fully characterized. Here, we perform an unbiased screen of 268 ISGs and identify Nectin4, also known as PVRL4, as a potent antiviral ISG against alphaherpesvirus, including herpes simplex virus (HSV). Mechanistically, Nectin4 inhibits viral internalization into host cells, in which the IgV domain plays a critical role. Specifically, Nectin4 interacts with the viral gD protein through this domain, thereby inhibiting the interaction between gD and viral receptor, Nectin1, and blocking gD-mediated viral entry. Together, our data identify a previously unrecognized function of Nectin4 in host anti-alphaherpesvirus immunity and highlight a novel cellular barrier that restricts alphaherpesvirus infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Interferon-stimulated genes (ISGs) are the major mediators of the host antiviral innate immunity, yet most remain functionally uncharacterized against alphaherpesviruses. Here, we identify interferon-stimulated Nectin4 (PVRL4) as a potent alphaherpesvirus restriction factor. By directly engaging the viral glycoprotein D (gD) and blocking its interaction with the entry receptor Nectin1, Nectin4 suppresses viral internalization. These findings broaden our understanding of the host-alphaherpesvirus interaction and highlight Nectin4 as a potential target for antiviral intervention against alphaherpesviruses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00788-26","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:00:46Z","timestamp":1784552446000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Nectin4 restricts pseudorabies virus infection by blocking gD-Nectin1 interaction"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6357-4974","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou 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