{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:28:45Z","timestamp":1788488925279,"version":"build-2803163510"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32330104"],"award-info":[{"award-number":["32330104"]}],"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":["32302956"],"award-info":[{"award-number":["32302956"]}],"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":["32461120064"],"award-info":[{"award-number":["32461120064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012228","name":"Shenzhen Municipal Development and Reform Commission","doi-asserted-by":"publisher","award":["XMHT20240215002"],"award-info":[{"award-number":["XMHT20240215002"]}],"id":[{"id":"10.13039\/501100012228","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026B1515020044"],"award-info":[{"award-number":["2026B1515020044"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>H5 highly pathogenic avian influenza viruses (HPAIVs) are prevalent in birds, causing infection in over 60 mammalian species worldwide. However, species-specific viral-host response at the single-cell level and within-host evolution upon H5 HPAIV infection are poorly understood. Here, by integrating spatial transcriptomics and single-cell genomics technologies, we present a comprehensive single-cell transcriptomic landscape of 1499\u2009669 cells in the lungs from birds (chickens, ducks, and pigeons) and mammals (mice and pigs) upon H5 HPAIV infection. H5 HPAIV primarily infected avian endothelial cells and mammalian epithelial cells, respectively. Among the single-cell transcriptomic lung landscape, H5 HPAIV infection induced significant inflammation in fibroblasts and the shedding of alveolar epithelial cells of chickens upon infection, while the expression levels of cytokine- and inflammation-related genes slightly decreased in fibroblasts and endothelial cells of infected ducks and pigeons, respectively. However, mice only exhibited significantly antiviral response in macrophages and neutrophils, while antiviral response was elevated in most subtype cells of pigs upon infection. Notably, we identified 19 viral non-synonymous intrahost single nucleotide variants in the infected birds and mammals and assessed their molecular characterizations in vitro. Three of them were identified to increase polymerase activity and viral replication in situ, among which the PB2-E627K mutation was enriched in the alveolar structure of lungs, accompanied by elevated expression of interferon-stimulated genes. Collectively, we elucidated distinct viral replication, host response, and viral adaptation in the lungs across diverse birds and mammals upon H5 HPAIV infection.<\/jats:p>","DOI":"10.1093\/nsr\/nwag380","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:45:15Z","timestamp":1782387915000},"source":"Crossref","is-referenced-by-count":1,"title":["Heterogeneous viral-host response at single-cell resolution and viral adaptive mutational atlas in birds and mammals upon H5 influenza virus infection"],"prefix":"10.1093","volume":"13","author":[{"given":"Jiahao","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"College of Veterinary Medicine, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"National Avian Influenza Para-Reference Laboratory , Guangzhou 510642 ,","place":["China"]},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control , Guangzhou 510642 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyuan","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"College of Veterinary Medicine, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Man","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"College of Veterinary Medicine, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"National Avian Influenza Para-Reference Laboratory , Guangzhou 510642 ,","place":["China"]},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control , Guangzhou 510642 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letian","family":"Li","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Changchun 130122 ,","place":["China"]},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control , Changchun 130122 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixing","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]},{"name":"College of Veterinary Medicine, Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiping","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqun","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 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Huazhong Agricultural University , Wuhan 430070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixin","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"National Avian Influenza Para-Reference Laboratory , Guangzhou 510642 ,","place":["China"]},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control , Guangzhou 510642 ,","place":["China"]},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province , Guangzhou 510642 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Shenzhen University of Advanced Technology , Shenzhen 518107 ,","place":["China"]},{"name":"Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518107 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["China"]},{"name":"National Avian Influenza Para-Reference Laboratory , Guangzhou 510642 ,","place":["China"]},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control , Guangzhou 510642 ,","place":["China"]},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province , Guangzhou 510642 ,","place":["China"]},{"name":"College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering , Guangzhou 510225 ,","place":["China"]},{"name":"Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences , Guangzhou 510640 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"2026081106170742300_bib1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1086\/338820","article-title":"Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997","volume":"34","author":"Chan","year":"2002","journal-title":"Clin Infect Dis"},{"key":"2026081106170742300_bib2","doi-asserted-by":"publisher","first-page":"veaa079","DOI":"10.1093\/ve\/veaa079","article-title":"Genetic diversity, phylogeography, and evolutionary dynamics of highly pathogenic avian influenza A (H5N6) 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