{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T07:35:53Z","timestamp":1768116953964,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Wildlife Disease Control and Prevention and the Ministry of Climate, Energy and Environment (MCEE) of South Korea","award":["2025-006"],"award-info":[{"award-number":["2025-006"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) grants funded by the Korean government","doi-asserted-by":"publisher","award":["RS-2024-00342230"],"award-info":[{"award-number":["RS-2024-00342230"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) grants funded by the Korean government","doi-asserted-by":"publisher","award":["RS-2024-00345119"],"award-info":[{"award-number":["RS-2024-00345119"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["2025-RISE-05-011"],"award-info":[{"award-number":["2025-RISE-05-011"]}]},{"name":"Korea Institute of Planning and Evaluation for Technology in Food","award":["RS-2025-0221738140982119420101"],"award-info":[{"award-number":["RS-2025-0221738140982119420101"]}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","award":["2024-GJ-RD-0033"],"award-info":[{"award-number":["2024-GJ-RD-0033"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses spread efficiently via migratory wild birds and increasingly infect mammals. The leopard cat (Prionailurus bengalensis) is an endangered mesopredator in South Korea that frequents wetland\u2013forest ecotones and overlaps with wild waterbirds, placing it at risk of exposure. We describe a fatal HPAI H5N1 infection in a free-ranging leopard cat detected through national wildlife surveillance during a period of widespread H5N1 activity in wild birds along the East Asian\u2013Australasian Flyway. The animal showed acute neurological and respiratory signs and died shortly after rescue. H5 viral RNA was detected by RT-qPCR in all examined tissues, with the highest load in the brain, and infectious virus was isolated from the brain, bronchoalveolar lavage fluid, and nasal swab. Pathology revealed acute serofibrinous pneumonia, severe nonsuppurative meningoencephalitis, necrotizing vasculitis with thrombosis, and necrotizing enteritis with secondary mesenteritis. Immunohistochemistry demonstrated abundant viral antigen in nasal and olfactory epithelium, olfactory bulb, neurons, endothelial cells, and bronchial and bronchiolar epithelium, supporting combined olfactory and hematogenous dissemination. This clinicopathological description expands the spectrum of HPAI-associated lesions in felids and underscores the value of wild carnivores as bioindicators of avian influenza spillover in a One Health context.<\/jats:p>","DOI":"10.3390\/ani16020200","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T16:03:16Z","timestamp":1767974596000},"page":"200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fatal H5N1 Highly Pathogenic Avian Influenza with Retrograde Neuroinvasion in a Free-Ranging Leopard Cat (Prionailurus bengalensis) During a Wild Bird Outbreak in South Korea"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9000-6901","authenticated-orcid":false,"given":"So-Hee","family":"Gwon","sequence":"first","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-0324","authenticated-orcid":false,"given":"Sang-Ik","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6397-9787","authenticated-orcid":false,"given":"Hyesung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daehun","family":"Kim","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaemoon","family":"Son","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-a","family":"Lee","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwanghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jae","family":"Si","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Jun","family":"Cho","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suwoong","family":"Lee","sequence":"additional","affiliation":[{"name":"Wildlife Disease Research Team, National Institute of Wildlife Disease Control and Prevention, Gwangju 62407, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0943-9297","authenticated-orcid":false,"given":"Hyeon Jeong","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5545-4464","authenticated-orcid":false,"given":"Gun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6049-049X","authenticated-orcid":false,"given":"Jaewoo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1029-5669","authenticated-orcid":false,"given":"Chung-Do","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Veterinary Zoonotic Diseases, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1703-7742","authenticated-orcid":false,"given":"Yeong-Bin","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1073\/pnas.1405216112","article-title":"Avian influenza H5N1 viral and bird migration networks in Asia","volume":"112","author":"Tian","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Graziosi, G., Lupini, C., Catelli, E., and Carnaccini, S. (2024). Highly Pathogenic Avian Influenza (HPAI) H5 Clade 2.3.4.4b Virus Infection in Birds and Mammals. Animals, 14.","DOI":"10.20944\/preprints202404.1123.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1080\/22221751.2021.1872355","article-title":"Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020","volume":"10","author":"Lewis","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e3255","DOI":"10.1111\/tbed.14551","article-title":"Emergence of clade 2.3.4.4b novel reassortant H5N1 high pathogenicity avian influenza virus in South Korea during late 2021","volume":"69","author":"Sagong","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"veae027","DOI":"10.1093\/ve\/veae027","article-title":"High pathogenic avian influenza A(H5) viruses of clade 2.3.4.4b in Europe-Why trends of virus evolution are more difficult to predict","volume":"10","author":"Fusaro","year":"2024","journal-title":"Virus Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1080\/22221751.2022.2088407","article-title":"Global dissemination of H5N1 influenza viruses bearing the clade 2.3.4.4b HA gene and biologic analysis of the ones detected in China","volume":"11","author":"Cui","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/03009858231222227","article-title":"Lesions and viral antigen distribution in bald eagles, red-tailed hawks, and great horned owls naturally infected with H5N1 clade 2.3.4.4b highly pathogenic avian influenza virus","volume":"61","author":"Torchetti","year":"2024","journal-title":"Vet. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41586-024-08054-z","article-title":"The global H5N1 influenza panzootic in mammals","volume":"637","author":"Peacock","year":"2025","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.3201\/eid3008.240481","article-title":"Highly Pathogenic Avian Influenza Virus A(H5N1) Clade 2.3.4.4b Infection in Free-Ranging Polar Bear, Alaska, USA","volume":"30","author":"Stimmelmayr","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1126\/science.1102287","article-title":"Avian H5N1 influenza in cats","volume":"306","author":"Kuiken","year":"2004","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"ofaf261","DOI":"10.1093\/ofid\/ofaf261","article-title":"Avian Influenza Virus Infections in Felines: A Systematic Review of Two Decades of Literature","volume":"12","author":"Coleman","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3201\/eid1204.051396","article-title":"Avian influenza H5N1 in naturally infected domestic cat","volume":"12","author":"Songserm","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.vetmic.2006.12.021","article-title":"Highly pathogenic avian influenza H5N1 virus in cats and other carnivores","volume":"122","author":"Thiry","year":"2007","journal-title":"Vet. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jcpa.2023.07.001","article-title":"Naturally occurring highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b infection in three domestic cats in North America during 2023","volume":"205","author":"Sillman","year":"2023","journal-title":"J. Comp. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.3201\/eid1412.080470","article-title":"Highly pathogenic avian influenza virus (H5N1) infection in red foxes fed infected bird carcasses","volume":"14","author":"Reperant","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ajpath.2011.03.026","article-title":"Pathogenesis of Influenza A\/H5N1 Virus Infection in Ferrets Differs between Intranasal and Intratracheal Routes of Inoculation","volume":"179","author":"Bodewes","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14063","DOI":"10.1073\/pnas.0900096106","article-title":"Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration","volume":"106","author":"Jang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Siegers, J.Y., Ferreri, L., Eggink, D., Kroeze, E.J.B.V., te Velthuis, A.J.W., van de Bildt, M., Leijten, L., van Run, P., de Meulder, D., and Bestebroer, T. (2023). Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011214"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vreman, S., Kik, M., Germeraad, E., Heutink, R., Harders, F., Spierenburg, M., Engelsma, M., Rijks, J., van den Brand, J., and Beerens, N. (2023). Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species. Pathogens, 12.","DOI":"10.3390\/pathogens12020168"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.tins.2023.08.002","article-title":"The neuropathogenesis of highly pathogenic avian influenza H5Nx viruses in mammalian species including humans","volume":"46","author":"Bauer","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e02867-22","DOI":"10.1128\/spectrum.02867-22","article-title":"Highly Pathogenic Avian Influenza H5N1 Virus Infections in Wild Red Foxes (Vulpes vulpes) Show Neurotropism and Adaptive Virus Mutations","volume":"11","author":"Bordes","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.3201\/eid3012.240154","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in Cats, South Korea, 2023","volume":"30","author":"Kang","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2290835","DOI":"10.1080\/22221751.2023.2290835","article-title":"Characterization of highly pathogenic avian influenza A (H5N1) viruses isolated from cats in South Korea, 2023","volume":"13","author":"Lee","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Si, Y.J., Lee, S.H., Kim, D.J., Lee, K., Lee, M.A., Lee, D.Y., Seo, Y.R., Jeong, H., Lee, S., and Lee, D.H. (2025). First detection of clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus in a wild leopard cat in South Korea. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1638067"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ji, C.P., Li, H.D., Xiao, W.H., Xu, K., Ren, Y.F., Li, H.Y., Wang, P.C., Fan, M.L., Huang, X.Q., and Xiao, Z.S. (2023). Fine-Scale Interactions between Leopard Cats and Their Potential Prey with Contrasting Diel Activities in a Livestock-Dominated Nature Reserve. Animals, 13.","DOI":"10.3390\/ani13081296"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, S., Lee, S., Song, W., and Lee, M.J. (2017). Habitat Potential Mapping of Marten and Leopard Cat in South Korea Using Artificial Neural Network Machine Learning. Appl. Sci., 7.","DOI":"10.3390\/app7090912"},{"key":"ref_27","first-page":"e00673","article-title":"Spatio-temporal characteristics and predictions of the endangered leopard cat road-kills in the Republic of Korea","volume":"19","author":"Kim","year":"2019","journal-title":"Glob. Ecol. Conserv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41392-022-01223-4","article-title":"Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus","volume":"7","author":"Baek","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1128\/JVI.06375-11","article-title":"Marked Endotheliotropism of Highly Pathogenic Avian Influenza Virus H5N1 following Intestinal Inoculation in Cats","volume":"86","author":"Reperant","year":"2012","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1128\/JVI.06828-11","article-title":"The Multibasic Cleavage Site in H5N1 Virus Is Critical for Systemic Spread along the Olfactory and Hematogenous Routes in Ferrets","volume":"86","author":"Schrauwen","year":"2012","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"176","DOI":"10.2353\/ajpath.2006.050466","article-title":"Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts","volume":"168","author":"Rimmelzwaan","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e02111-24","DOI":"10.1128\/mbio.02111-24","article-title":"Broadening the aims of avian influenza surveillance according to the One Health approach","volume":"15","author":"Kuiken","year":"2024","journal-title":"Mbio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100760","DOI":"10.1016\/j.onehlt.2024.100760","article-title":"Assessing avian influenza surveillance intensity in wild birds using a One Health lens","volume":"18","author":"Giacinti","year":"2024","journal-title":"One Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10884","DOI":"10.1128\/JVI.01016-13","article-title":"Mammalian Adaptation in the PB2 Gene of Avian H5N1 Influenza Virus","volume":"87","author":"Min","year":"2013","journal-title":"J. Virol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/2\/200\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T05:11:01Z","timestamp":1768108261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/2\/200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ani16020200"],"URL":"https:\/\/doi.org\/10.3390\/ani16020200","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}