{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:37:38Z","timestamp":1788187058805,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2022R1026005"],"award-info":[{"award-number":["2022R1026005"]}],"id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2022J01466"],"award-info":[{"award-number":["2022J01466"]}],"id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018914","name":"Fujian Academy of Agricultural Sciences","doi-asserted-by":"publisher","award":["YCZX202412"],"award-info":[{"award-number":["YCZX202412"]}],"id":[{"id":"10.13039\/501100018914","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018914","name":"Fujian Academy of Agricultural Sciences","doi-asserted-by":"publisher","award":["CXTD2021005-1"],"award-info":[{"award-number":["CXTD2021005-1"]}],"id":[{"id":"10.13039\/501100018914","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018914","name":"Fujian Academy of Agricultural Sciences","doi-asserted-by":"publisher","award":["KJZD2025002"],"award-info":[{"award-number":["KJZD2025002"]}],"id":[{"id":"10.13039\/501100018914","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Hypervirulent fowl adenovirus serotype 4 (FAdV-4) has emerged as a significant poultry pathogen since 2015, exhibiting clinical multi-organ and multi-tissue tropism post-infection, resulting in substantial economic losses in the poultry industry. However, the molecular mechanism underlying kidney injury caused by FAdV-4 infection remains unclear. Our results indicated that FAdV-4 infection in chickens induces damage to kidney tissues, characterized by the degeneration and necrosis of kidney epithelial cells, glomerular injury, endoplasmic reticulum stress, and the activation of a robust inflammatory response in the kidney cells. Notably, autophagosome-like vesicles enclosed clusters of viral particles that were transmitted between kidney cells post-infection. There might be a novel mechanism of vesicle-mediated cell-to-cell transmission of hypervirulent FAdV-4 that hijacks autophagosome-like vesicles. We also investigated cellular autophagy in kidney cells\n              <jats:italic>in vivo<\/jats:italic>\n              and\n              <jats:italic>in vitro<\/jats:italic>\n              during early FAdV-4 infection. The autophagy-related marker proteins LC3B, ATG5, and BECN1 were upregulated post-infection, whereas SQSTM1 was downregulated, indicating that FAdV-4 infection enhances autophagic flux and induces complete autophagy. The viral structural protein Fiber 2 was also observed to colocalize with the autophagy-related marker protein LC3B and the exosome-specific marker protein CD63 in the kidney cells at 24 hpi, suggesting that FAdV-4-induced cellular autophagy promotes viral replication in kidney cells and that autophagosome-like vesicles are involved in early FAdV-4 replication\n              <jats:italic>in vivo<\/jats:italic>\n              in chickens. Our results offer novel insights into the pathogenesis of hypervirulent FAdV-4 from the perspective of kidney injury post-infection.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Hypervirulent fowl adenovirus serotype 4 (FAdV-4) has become globally prevalent since 2015 as a predominant pathogen on poultry farms, leading to substantial economic losses for the poultry industry. However, the molecular mechanisms underlying kidney injury induced by FAdV-4 infection remain unclear. In this study, we primarily elucidated the mechanisms of kidney injury induced by FAdV-4 infection in chickens, utilizing both\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              models. Our results demonstrate that FAdV-4 infection in chickens causes degeneration and necrosis of kidney epithelial cells, glomerular injury, and expansion of the endoplasmic reticulum, while also triggering a robust inflammatory response in kidney cells. Notably, we observed the cell-to-cell transmission of virus particles delivered by autophagosome-like vesicles, and the viral infection-induced cellular autophagy facilitated viral replication in the kidney cells. These findings offer a novel perspective to understand the molecular mechanisms of FAdV-4-induced kidney injury and establish a basis for further investigation into the molecular pathogenesis of hypervirulent FAdV-4.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00058-25","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T15:50:49Z","timestamp":1742917849000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic insights into the kidney injury in chickens induced by hypervirulent fowl adenovirus serotype 4"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-4311","authenticated-orcid":true,"given":"Chunhua","family":"Zhu","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory for Avian Diseases Control and Prevention, Institute of Animal Husbandry and Veterinary Medicine, 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