{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:44:25Z","timestamp":1784335465619,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The highly pathogenic avian influenza H5N1 2.3.4.4b clade virus has caused widespread outbreaks across South America, primarily affecting seabirds, poultry, and marine mammals. The virus likely reached the continent through migratory birds from North America, initially spreading along the Pacific coast before advancing into Atlantic-bordering countries such as Argentina, Uruguay, and Brazil. This study investigated the dynamics of H5N1 strains in Uruguay during outbreaks from February and October 2023. We analyzed an updated South American database, including a newly sequenced viral genome from a royal tern (Thalasseus maximus) collected at the end of the outbreaks. Phylogeographic reconstruction revealed two distinct South American phylogroups comprising Uruguayan strains: one mainly driven by wild birds and poultry, with the royal tern strain clustering with Brazilian isolates, and another primarily associated with marine mammals, displaying adaptive residues in the PB2 protein. In Uruguay, these phylogroups delineate two main transmission routes: (i) an avian-derived pathway originating in Argentina and (ii) a pinniped-derived route from Chile. Brazil, initially colonized via the Argentine route, later emerged as a secondary source for Uruguay. This host-pathway interplay underscores the virus\u2019s cross-species potential and highlights the need for coordinated regional surveillance within a One Health framework to mitigate zoonotic risks.<\/jats:p>","DOI":"10.3390\/pathogens14080793","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T11:41:53Z","timestamp":1754653313000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Converging Transmission Routes of the Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b Virus in Uruguay: Phylogeographic Insights into Its Spread Across South America"],"prefix":"10.3390","volume":"14","author":[{"given":"Ana","family":"Marandino","sequence":"first","affiliation":[{"name":"Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-2046","authenticated-orcid":false,"given":"Gonzalo","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7459-7810","authenticated-orcid":false,"given":"Yanina","family":"Panzera","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Williman","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-3456","authenticated-orcid":false,"given":"Filipe Zimmer","family":"Dezordi","sequence":"additional","affiliation":[{"name":"Instituto Aggeu Magalh\u00e3es (IAM)-Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Recife 50670-420, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-5713","authenticated-orcid":false,"given":"Gabriel Luz","family":"Wallau","sequence":"additional","affiliation":[{"name":"Instituto Aggeu Magalh\u00e3es (IAM)-Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Recife 50670-420, Brazil"},{"name":"Bernhard Nocht Institute for Tropical Medicine, National Reference Center for Tropical Infectious Diseases, WHO Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, D-20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirley","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Laboratorios Veterinarios \u201cMiguel C. Rubino\u201d, Direcci\u00f3n General de Servicios Ganaderos, Ministerio de Ganader\u00eda, Agriculturay Pesca, Montevideo 12100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Laboratorios Veterinarios \u201cMiguel C. Rubino\u201d, Direcci\u00f3n General de Servicios Ganaderos, Ministerio de Ganader\u00eda, Agriculturay Pesca, Montevideo 12100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Bassetti","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Laboratorios Veterinarios \u201cMiguel C. Rubino\u201d, Direcci\u00f3n General de Servicios Ganaderos, Ministerio de Ganader\u00eda, Agriculturay Pesca, Montevideo 12100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Negro","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Laboratorios Veterinarios \u201cMiguel C. Rubino\u201d, Direcci\u00f3n General de Servicios Ganaderos, Ministerio de Ganader\u00eda, Agriculturay Pesca, Montevideo 12100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n Nacional de Biodiversidad y Servicios Ecosist\u00e9micos (DINABISE), Ministerio de Ambiente, Montevideo 11100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Leizagoyen","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n Nacional de Biodiversidad y Servicios Ecosist\u00e9micos (DINABISE), Ministerio de Ambiente, Montevideo 11100, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4961-4743","authenticated-orcid":false,"given":"Ruben","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1006\/viro.1999.9820","article-title":"Genetic Characterization of the Pathogenic Influenza A\/Goose\/Guangdong\/1\/96 (H5N1) Virus: Similarity of Its Hemagglutinin Gene to Those of H5N1 Viruses from the 1997 Outbreaks in Hong Kong","volume":"261","author":"Xu","year":"1999","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/irv.12324","article-title":"Nomenclature Updates Resulting from the Evolution of Avian Influenza A (H5) Virus Clades 2.1.3.2a, 2.2.1, and 2.3.4 during 2013\u20132014","volume":"9","author":"Smith","year":"2015","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_3","first-page":"e07917","article-title":"Avian Influenza Overview December 2022\u2013March 2023","volume":"21","author":"Adlhoch","year":"2023","journal-title":"EFSA J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and Evolution of Pathogenic Coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109860","DOI":"10.1016\/j.virol.2023.109860","article-title":"H5N1 Highly Pathogenic Avian Influenza Clade 2.3.4.4b in Wild and Domestic Birds: Introductions into the United States and Reassortments, December 2021\u2013April 2022","volume":"587","author":"Youk","year":"2023","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4142\/jvs.2017.18.S1.269","article-title":"Evolution, Global Spread, and Pathogenicity of Highly Pathogenic Avian Influenza H5Nx Clade 2.3.4.4","volume":"18","author":"Lee","year":"2017","journal-title":"J. Vet. Sci."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"e774","DOI":"10.1016\/S1473-3099(24)00438-9","article-title":"The Panzootic Spread of Highly Pathogenic Avian Influenza H5N1 Sublineage 2.3.4.4b: A Critical Appraisal of One Health Preparedness and Prevention","volume":"24","author":"Koopmans","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00052-25","DOI":"10.1128\/jvi.00052-25","article-title":"Pandemic Risk Stemming from the Bovine H5N1 Outbreak: An Account of the Knowns and Unknowns","volume":"99","author":"Lowen","year":"2025","journal-title":"J. Virol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"7433","DOI":"10.1038\/s41467-024-51490-8","article-title":"Detection and Spread of High Pathogenicity Avian Influenza Virus H5N1 in the Antarctic Region","volume":"15","author":"Banyard","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bennett-Laso, B., Berazay, B., Mu\u00f1oz, G., Ariyama, N., Enciso, N., Braun, C., Kr\u00fcger, L., Bart\u00e1k, M., Gonz\u00e1lez-Aravena, M., and Neira, V. (2024). Confirmation of Highly Pathogenic Avian Influenza H5N1 in Skuas, Antarctica 2024. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1423404"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kuiken, T., Vanstreels, R.E.T., Banyard, A., Begeman, L., Breed, A.C., Dewar, M., Fijn, R., Serafini, P.P., Uhart, M., and Wille, M. (2025). Emergence, Spread, and Impact of High-pathogenicity Avian Influenza H5 in Wild Birds and Mammals of South America and Antarctica. Conserv. Biol., 31.","DOI":"10.1111\/cobi.70052"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.3201\/eid3007.240717","article-title":"Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA","volume":"30","author":"Oguzie","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1007\/s10096-025-05147-z","article-title":"The Emergence of Highly Pathogenic Avian Influenza H5N1 in Dairy Cattle: Implications for Public Health, Animal Health, and Pandemic Preparedness","volume":"44","author":"Kamel","year":"2025","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.15585\/mmwr.mm7315a1","article-title":"Heat-Related Emergency Department Visits\u2014United States, May\u2013September 2023","volume":"73","author":"Vaidyanathan","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Castro-Sanguinetti, G.R., Gonz\u00e1lez-Veliz, R., Callupe-Leyva, A., Apaza-Chiara, A.P., Jara, J., Silva, W., Icochea, E., and More-Bayona, J.A. (2024). Highly Pathogenic Avian Influenza Virus H5N1 Clade 2.3.4.4b from Peru Forms a Monophyletic Group with Chilean Isolates in South America. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-54072-2"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Marandino, A., Tom\u00e1s, G., Panzera, Y., Leizagoyen, C., P\u00e9rez, R., Bassetti, L., Negro, R., Rodr\u00edguez, S., and P\u00e9rez, R. (2023). Spreading of the High-Pathogenicity Avian Influenza (H5N1) Virus of Clade 2.3.4.4b into Uruguay. Viruses, 15.","DOI":"10.3390\/v15091906"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1038\/s41467-025-57338-z","article-title":"Cross-Species and Mammal-to-Mammal Transmission of Clade 2.3.4.4b Highly Pathogenic Avian Influenza A\/H5N1 with PB2 Adaptations","volume":"16","author":"Nelson","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gamarra-Toledo, V., Plaza, P.I., Angulo, F., Guti\u00e9rrez, R., Garc\u00eda-Tello, O., Saravia-Guevara, P., Mej\u00eda-Vargas, F., Epiqui\u00e9n-Rivera, M., Quiroz-Jim\u00e9nez, G., and Martinez, P. (2023). Highly Pathogenic Avian Influenza (HPAI) Strongly Impacts Wild Birds in Peru. Biol. Conserv., 286.","DOI":"10.1016\/j.biocon.2023.110272"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106895","DOI":"10.1016\/j.micpath.2024.106895","article-title":"Infection of South American Coatis (Nasua Nasua) with Highly Pathogenic Avian Influenza H5N1 Virus Displaying Mammalian Adaptive Mutations","volume":"195","author":"Marandino","year":"2024","journal-title":"Microb. Pathog."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"veae031","DOI":"10.1093\/ve\/veae031","article-title":"Highly Pathogenic Avian Influenza H5N1 Virus Infections in Pinnipeds and Seabirds in Uruguay: Implications for Bird-Mammal Transmission in South America","volume":"10","author":"Marandino","year":"2024","journal-title":"Virus Evol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2023.2265173","article-title":"Mass Mortality Event in South American Sea Lions (Otaria Flavescens) Correlated to Highly Pathogenic Avian Influenza (HPAI) H5N1 Outbreak in Chile","volume":"43","author":"Ulloa","year":"2023","journal-title":"Vet. Q."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3201\/eid3003.231098","article-title":"Recent Changes in Patterns of Mammal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus Worldwide","volume":"30","author":"Plaza","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: Pairwise Alignment for Nucleotide Sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"30494","DOI":"10.2807\/1560-7917.ES.2017.22.13.30494","article-title":"GISAID: Global Initiative on Sharing All Influenza Data\u2013from Vision to Reality","volume":"22","author":"Shu","year":"2017","journal-title":"Eurosurveillance"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1093\/bioinformatics\/bty407","article-title":"Nextstrain: Real-Time Tracking of Pathogen Evolution","volume":"34","author":"Hadfield","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.21105\/joss.02906","article-title":"Augur: A Bioinformatics Toolkit for Phylogenetic Analyses of Human Pathogens","volume":"6","author":"Huddleston","year":"2021","journal-title":"JOSS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"vex042","DOI":"10.1093\/ve\/vex042","article-title":"TreeTime: Maximum-Likelihood Phylodynamic Analysis","volume":"4","author":"Sagulenko","year":"2018","journal-title":"Virus Evol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5489","DOI":"10.1038\/s41467-023-41182-0","article-title":"Highly Pathogenic Avian Influenza A (H5N1) in Marine Mammals and Seabirds in Peru","volume":"14","author":"Leguia","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9516","DOI":"10.1038\/s41467-024-53766-5","article-title":"Epidemiological Data of an Influenza A\/H5N1 Outbreak in Elephant Seals in Argentina Indicates Mammal-to-Mammal Transmission","volume":"15","author":"Uhart","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.3201\/eid2909.230067","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Wild Birds, Chile","volume":"29","author":"Ariyama","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102591","DOI":"10.1016\/j.tmaid.2023.102591","article-title":"Multiple Introductions of Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b into South America","volume":"53","author":"Pujol","year":"2023","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vanstreels, R.E.T., Nelson, M.I., Artuso, M.C., Marchione, V.D., Piccini, L.E., Benedetti, E., Crespo-Bellido, A., Pierdomenico, A., Wolff, T., and Uhart, M. (2025). Novel Highly Pathogenic Avian Influenza (A)H5N1 Triple Reassortant in Argentina. bioRXiv, bioRXiv:2025.05.23.655175.","DOI":"10.1101\/2025.05.23.655175"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Piaggio, A.J., Shriner, S.A., VanDalen, K.K., Franklin, A.B., Anderson, T.D., and Kolokotronis, S.-O. (2012). Molecular Surveillance of Low Pathogenic Avian Influenza Viruses in Wild Birds across the United States: Inferences from the Hemagglutinin Gene. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050834"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Artuso, M.C., Marchione, V.D., Benedetti, E., Bonastre, P., Alvarez, A.M., Piccini, L., Ponde, A., Barrios Benito, E., Fabeiro, M., and Waisman, K. (2024). Detection and Characterization of Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.4.4b Virus Circulating in Argentina in 2023. Rev. Argent. Microbiol., in press.","DOI":"10.1016\/j.ram.2024.08.002"},{"key":"ref_39","first-page":"2300109","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in Farmed Minks, Spain, October 2022","volume":"28","author":"Monne","year":"2023","journal-title":"Eurosurveillance"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/s41586-024-08063-y","article-title":"H5N1 Clade 2.3.4.4b Dynamics in Experimentally Infected Calves and Cows","volume":"637","author":"Halwe","year":"2025","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2380421","DOI":"10.1080\/22221751.2024.2380421","article-title":"Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle","volume":"13","author":"Hu","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, W., Lee, H.H.Y., Li, R.F., Zhu, H.M., Yi, G., Peiris, J.S.M., Yang, Z.F., and Mok, C.K.P. (2017). The PB2 Mutation with Lysine at 627 Enhances the Pathogenicity of Avian Influenza (H7N9) Virus Which Belongs to a Non-Zoonotic Lineage. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02598-z"},{"key":"ref_43","first-page":"619","article-title":"Incursion of Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus, Brazil, 2023","volume":"30","author":"Silva","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"199415","DOI":"10.1016\/j.virusres.2024.199415","article-title":"Phylodynamics of Avian Influenza A(H5N1) Viruses from Outbreaks in Brazil","volume":"347","author":"Rivetti","year":"2024","journal-title":"Virus Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10691","DOI":"10.1128\/JVI.00786-11","article-title":"Reversion of PB2-627E to -627K during Replication of an H5N1 Clade 2.2 Virus in Mammalian Hosts Depends on the Origin of the Nucleoprotein","volume":"85","author":"Bogs","year":"2011","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18590","DOI":"10.1073\/pnas.0507415102","article-title":"The Viral Polymerase Mediates Adaptation of an Avian Influenza Virus to a Mammalian Host","volume":"102","author":"Gabriel","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gao, Y., Zhang, Y., Shinya, K., Deng, G., Jiang, Y., Li, Z., Guan, Y., Tian, G., Li, Y., and Shi, J. (2009). Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000709"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9641","DOI":"10.1128\/JVI.00702-11","article-title":"Amino Acid Residues 253 and 591 of the PB2 Protein of Avian Influenza Virus A H9N2 Contribute to Mammalian Pathogenesis","volume":"85","author":"Mok","year":"2011","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhu, W., Li, L., Yan, Z., Gan, T., Li, L., Chen, R., Chen, R., Zheng, Z., Hong, W., and Wang, J. (2015). Dual E627K and D701N Mutations in the PB2 Protein of A(H7N9) Influenza Virus Increased Its Virulence in Mammalian Models. Sci. Rep., 5.","DOI":"10.1038\/srep14170"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pal\u00f9, G., Roggero, P.F., and Calistri, A. (2024). Could H5N1 Bird Flu Virus Be the Cause of the next Human Pandemic?. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1477738"},{"key":"ref_51","unstructured":"PAHO\/WHO (2025). Epidemiological Update Avian Influenza A (H5N1) in the Americas Region, PAHO\/WHO."},{"key":"ref_52","unstructured":"Billerman, S.M. (2021). Royal Tern (Thalasseus maximus). Birds of the World, Cornell Lab of Ornithology."},{"key":"ref_53","unstructured":"Del Hoyo, J., Elliott, A., Sargatal, J., Christie, D., De Juana, E., and Medrano, F. (2024). South American Tern (Sterna hirundinacea). Birds of the World, Cornell Lab of Ornithology."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/793\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:26:29Z","timestamp":1760034389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["pathogens14080793"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14080793","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]}}}