{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:51:57Z","timestamp":1786117917793,"version":"build-2736575974"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Scientific Research Innovation Capability Support Project for Young Faculty","award":["ZYGXQNJSKYCXNLZCXM-A4"],"award-info":[{"award-number":["ZYGXQNJSKYCXNLZCXM-A4"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473031, 32122086"],"award-info":[{"award-number":["32473031, 32122086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2662025DKPY009, 2662025PY001"],"award-info":[{"award-number":["2662025DKPY009, 2662025PY001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010038","name":"Earmarked Fund for China Agriculture Research System","doi-asserted-by":"publisher","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}],"id":[{"id":"10.13039\/501100010038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Pseudorabies virus (PRV), the etiological agent of Aujeszky\u2019s disease, remains a major threat to the swine industry. Several human PRV infections have recently been reported, including cases with severe ocular involvement, but how human-derived PRV isolates injure retinal cells remains poorly understood. Here, we used the human-derived PRV isolate hSD-1\/2019 and ARPE-19 cells to define an injury-associated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling pathway in retinal epithelial cells. hSD-1\/2019 infection induced pronounced extracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, CaMKII and JNK1\/2 activation, mitochondrial dysfunction, and membrane-compromising cellular injury. Pharmacological screening identified a prominent Cav2.2-sensitive component in the infection-associated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx. Blockade of this component attenuated JNK1\/2 activation, mitochondrial injury, and loss of membrane integrity, linking extracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      entry to downstream epithelial injury. In addition, PRV glycoprotein K (gK) expression promoted Cav2.2-sensitive Ca\n                      <jats:sup>2+<\/jats:sup>\n                      elevation and JNK1\/2 activation in transfected cells, supporting gK as a candidate upstream viral contributor to this response. Together, these findings suggest that hSD-1\/2019 converts infection into a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx-driven injury program in retinal epithelial cells and identify a Cav2.2-sensitive Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/JNK axis as a focused mechanism of PRV-associated retinal epithelial injury.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Pseudorabies virus (PRV) has long been considered primarily an animal pathogen, but recent human infections with severe ocular disease have raised concerns about its ability to damage human retinal cells. This study shows that the human-derived PRV isolate hSD-1\/2019 engages extracellular Ca\n                        <jats:sup>2+<\/jats:sup>\n                        influx to drive a JNK1\/2-linked mitochondrial injury response in ARPE-19 cells. A Cav2.2-sensitive Ca\n                        <jats:sup>2+<\/jats:sup>\n                        entry component was functionally associated with this process, and PRV gK was identified as a candidate viral contributor capable of engaging the Ca\n                        <jats:sup>2+<\/jats:sup>\n                        \/JNK response. These findings provide a mechanistic framework for PRV-associated retinal epithelial injury and support further investigation in primary retinal cells and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        models.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01655-26","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:02:18Z","timestamp":1784206938000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A human-derived Pseudorabies virus isolate induces Cav2.2-sensitive Ca\n                    <sup>2+<\/sup>\n                    influx and JNK-associated retinal epithelial injury"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2820-6770","authenticated-orcid":false,"given":"Chuyue","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University","place":["Wuhan, China"]},{"name":"Key Laboratory of 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