{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:16:50Z","timestamp":1791159410759,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam Bin Abdulaziz University","doi-asserted-by":"publisher","award":["(PSAU\/2025\/03\/37151)"],"award-info":[{"award-number":["(PSAU\/2025\/03\/37151)"]}],"id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]},{"award":["(PSAU\/2025\/03\/37151)"],"award-info":[{"award-number":["(PSAU\/2025\/03\/37151)"]}],"id":[{"id":"https:\/\/ror.org\/04jt46d36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk.<\/jats:p>","DOI":"10.3390\/v18040410","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:36:40Z","timestamp":1774532200000},"page":"410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Deciphering HPAI Influenza A Virus (H5N1): Molecular Basis of Pathogenicity, Zoonotic Potential, and Advances in Vaccination Strategies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0684-3550","authenticated-orcid":false,"given":"Imran","family":"Mohammad","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4017-7292","authenticated-orcid":false,"given":"Mohammed Ibrahim","family":"Hajelbashir","sequence":"additional","affiliation":[{"name":"Department of Pediatric, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-4442","authenticated-orcid":false,"given":"Mahmoud H.","family":"El-Bidawy","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-2706","authenticated-orcid":false,"given":"Abdulwahab","family":"Abuderman","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murtaja","family":"Satea","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Warith Al-Anbiyaa, Karbala 56001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M. R.","family":"Arafah","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Rizwan","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahjabeen","family":"Rahmani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Commerce, Arts & Science, Patliputra University, KankarBagh, Patna 800020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-8360","authenticated-orcid":false,"given":"Mohiuddin Khan","family":"Warsi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 23890, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-1440","authenticated-orcid":false,"given":"Nawal","family":"Helmi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-3441","authenticated-orcid":false,"given":"Mohammad Azhar","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","unstructured":"Wong, S.Y.H. (2015). Highly Pathogenic Avian Influenza (H5N1) in Hong Kong, 1997\u20132014: Towards an Urban Biopolitical Immunology. [Ph.D. Thesis, The University of Manchester]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8950","DOI":"10.1073\/pnas.132268999","article-title":"Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR","volume":"99","author":"Guan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e0060922","DOI":"10.1128\/mbio.00609-22","article-title":"Has epizootic become enzootic? Evidence for a fundamental change in the infection dynamics of highly pathogenic avian influenza in Europe, 2021","volume":"13","author":"Pohlmann","year":"2022","journal-title":"mBio"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Caserta, L.C., Frye, E.A., Butt, S.L., Laverack, M., Nooruzzaman, M., Covaleda, L.M., Thompson, A.C., Prarat Koscielny, M., Cronk, B., and Johnson, A. (2024). From birds to mammals: Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle led to efficient intra-and interspecies transmission. bioRxiv.","DOI":"10.1101\/2024.05.22.595317"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Everest, H., Hill, S.C., Daines, R., Sealy, J.E., James, J., Hansen, R., and Iqbal, M. (2020). The evolution, spread and global threat of H6Nx avian influenza viruses. Viruses, 12.","DOI":"10.3390\/v12060673"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.cmi.2016.07.007","article-title":"Functional balance between neuraminidase and haemagglutinin in influenza viruses","volume":"22","author":"Gaymard","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"de Bruin, A.C., Funk, M., Spronken, M.I., Gultyaev, A.P., Fouchier, R.A., and Richard, M. (2022). Hemagglutinin subtype specificity and mechanisms of highly pathogenic avian influenza virus genesis. Viruses, 14.","DOI":"10.3390\/v14071566"},{"key":"ref_8","unstructured":"Cairns Queensland Australia (2004). Abstracts of papers presented at the Asia-Pacific forum on tropical health innovation, incorporating the annual scientific meeting of the ACTM, and the Australian centre for international and tropical health and nutritiona. Ann. ACTM Int. J. Trop. Travel Med., 5, 24\u201338."},{"key":"ref_9","first-page":"15","article-title":"A review on avian influenza and its economic and public health impact","volume":"4","author":"Gashaw","year":"2020","journal-title":"Int. J. Vet. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/10408410701647594","article-title":"The human\/animal interface: Emergence and resurgence of zoonotic infectious diseases","volume":"33","author":"Greger","year":"2007","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e14389","DOI":"10.1111\/1751-7915.14389","article-title":"Avian influenza virus cross-infections as test case for pandemic preparedness: From epidemiological hazard models to sequence-based early viral warning systems","volume":"17","year":"2024","journal-title":"Microb. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Suttie, A., Tok, S., Yann, S., Keo, P., Horm, S.V., Roe, M., Kaye, M., Sorn, S., Holl, D., and Tum, S. (2019). Diversity of A (H5N1) clade 2.3. 2.1 c avian influenza viruses with evidence of reassortment in Cambodia, 2014\u20132016. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226108"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4065\/79.4.523","article-title":"Avian influenza: A new pandemic threat?","volume":"Volume 79","author":"Trampuz","year":"2004","journal-title":"Mayo Clinic Proceedings"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3201\/eid2203.150593","article-title":"Avian Influenza A(H5N1) Virus in Egypt","volume":"22","author":"Kayali","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a038745","DOI":"10.1101\/cshperspect.a038745","article-title":"H5 Influenza Viruses in Egypt","volume":"11","author":"Kandeil","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1080\/00063657.2024.2396563","article-title":"A case study of highly pathogenic avian influenza (HPAI) H5N1 at Bird Island, South Georgia: The first documented outbreak in the subantarctic region","volume":"71","author":"Bennison","year":"2024","journal-title":"Bird Study"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s44298-025-00138-5","article-title":"Highly pathogenic avian influenza H5N1 in the United States: Recent incursions and spillover to cattle","volume":"3","author":"Mostafa","year":"2025","journal-title":"NPJ Viruses"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1038\/s41467-025-61757-3","article-title":"Genotype B3. 13 influenza A (H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties","volume":"16","author":"Fabrizio","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"El-Bidawy, M.H., Mohammad, I., Ansari, M.R., Hajelbashir, M.I., Khan, M.S., Poyil, M.M., Bari, M.N., Arafah, A.M., Kamal, M.A., and Ahsan, S.T.M. (2026). Highly Pathogenic Avian Influenza: Tracking the Progression from IAV (H5N1) to IAV (H7N9) and Preparing for Emerging Challenges. Microorganisms, 14.","DOI":"10.3390\/microorganisms14010012"},{"key":"ref_20","first-page":"2300201","article-title":"The highly pathogenic avian influenza A (H5N1) virus of clade 2.3.4.4b in Europe: A narrative review","volume":"28","author":"Claes","year":"2023","journal-title":"Eurosurveillance"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/s41586-023-06631-2","article-title":"The episodic resurgence of highly pathogenic avian influenza H5 virus","volume":"622","author":"Xie","year":"2023","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109860","DOI":"10.1016\/j.virol.2023.109860","article-title":"H5N1 highly pathogenic avian influenza clade 2.3. 4.4 b 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_23","unstructured":"US Department of Agriculture, Animal and Plant Health Inspection Service (USDA APHIS) (2023). 2022\u20132023 Confirmations of Highly Pathogenic Avian Influenza in Commercial and Backyard Flocks."},{"key":"ref_24","unstructured":"Canadian Food Inspection Agency (CFIA) (2025). 2025 Report: HPAI in Canada\u2014Epidemiology and Impact."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (EFSA), European Centre for Disease Prevention and Control (ECDC), and European Union Reference Laboratory for Avian Influenza (2023). Scientific report: Avian influenza overview December 2022\u2013March 2023. EFSA J., 21, 7917.","DOI":"10.2903\/j.efsa.2023.7917"},{"key":"ref_26","unstructured":"Kuchler, F., and Risdon, R. (2023). Economic and Market Impacts of HPAI Outbreaks in the United States."},{"key":"ref_27","first-page":"2300001","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_28","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_29","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.3201\/eid3007.240508","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024","volume":"30","author":"Burrough","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.1999.9716","article-title":"Role of hemagglutinin cleavage for the pathogenicity of influenza virus","volume":"258","author":"Steinhauer","year":"1999","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1128\/CMR.14.1.129-149.2001","article-title":"Pandemic threat posed by avian influenza A viruses","volume":"14","author":"Horimoto","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1242917","article-title":"Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses","volume":"342","author":"Shi","year":"2013","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1126\/science.1213362","article-title":"Airborne transmission of influenza A\/H5N1 virus between ferrets","volume":"336","author":"Herfst","year":"2012","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1128\/jvi.67.4.1761-1764.1993","article-title":"A single amino acid in the PB2 gene of influenza A virus is a determinant of host range","volume":"67","author":"Subbarao","year":"1993","journal-title":"J. Virol."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1038\/s41467-023-38415-7","article-title":"Rapid evolution of A (H5N1) influenza viruses after intercontinental spread to North America","volume":"14","author":"Kandeil","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_37","unstructured":"World Health Organization (WHO) Cumulative Number of Confirmed Human Cases for Avian Influenza A(H5N1) Reported to WHO, 2003\u20132025."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1056\/NEJMc2405371","article-title":"Highly pathogenic avian influenza A(H5N1) virus infection in a dairy farm worker","volume":"390","author":"Uyeki","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00621-25","DOI":"10.1128\/jvi.00621-25","article-title":"Dairy cattle herds mount a characteristic antibody response to highly pathogenic H5N1 avian influenza viruses","volume":"99","author":"Simmons","year":"2025","journal-title":"J. Virol."},{"key":"ref_40","unstructured":"Finnish Institute for Health and Welfare (THL) (2024). Vaccination Against Avian Influenza for At-Risk Groups Began\u2014Good Protection Achieved."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41564-018-0296-2","article-title":"Tracking virus outbreaks in the twenty-first century","volume":"4","author":"Grubaugh","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2515135518821625","DOI":"10.1177\/2515135518821625","article-title":"A review of H5Nx avian influenza viruses","volume":"7","author":"Nunez","year":"2019","journal-title":"Ther. Adv. Vaccines Immunother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1637\/10183-041012-Review.1","article-title":"Impact of vaccines and vaccination on global control of avian influenza","volume":"56","author":"Swayne","year":"2012","journal-title":"Avian Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.virol.2015.03.009","article-title":"Transmission of influenza A viruses","volume":"479\u2013480","author":"Neumann","year":"2015","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority, European Centre for Disease Prevention and Control, European Union Reference Laboratory for Avian Influenza, Fusaro, A., Gonzales, J.L., Kuiken, T., Mirinavi\u010di\u016bt\u0117, G., Niqueux, \u00c9., St\u00e5hl, K., and Staubach, C. (2024). Avian influenza overview December 2023\u2013March 2024. EFSA J., 22, 8754.","DOI":"10.2903\/j.efsa.2024.8754"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1073\/pnas.1524384113","article-title":"Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein","volume":"113","author":"Russier","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/ncomms1158","article-title":"Differential use of importin-\u03b1 isoforms governs cell tropism and host adaptation of influenza virus","volume":"2","author":"Gabriel","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature16474","article-title":"Species difference in ANP32A underlies influenza A virus polymerase host restriction","volume":"529","author":"Long","year":"2016","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1006\/viro.1998.9508","article-title":"Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems","volume":"252","author":"Egorov","year":"1998","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/nm757","article-title":"Lethal H5N1 influenza viruses escape host anti-viral cytokine responses","volume":"8","author":"Seo","year":"2002","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zamarin, D., Garcia-Sastre, A., Xiao, X., Wang, R., and Palese, P. (2005). Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog., 1.","DOI":"10.1371\/journal.ppat.0010004"},{"key":"ref_52","first-page":"843","article-title":"The special neuraminidase stalk of highly pathogenic avian influenza virus H5N1 is critical for its biological properties","volume":"83","author":"Zhou","year":"2009","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Blagodatski, A., Trutneva, K., Glazova, O., Mityaeva, O., Shevkova, L., Kegeles, E., Onyanov, N., Fede, K., Maznina, A., and Khavina, E. (2021). Avian influenza in wild birds and poultry: Dissemination pathways, monitoring methods, and virus ecology. Pathogens, 10.","DOI":"10.3390\/pathogens10050630"},{"key":"ref_54","first-page":"12804","article-title":"The role of nucleoprotein in influenza A virus host adaptation","volume":"83","author":"Smith","year":"2009","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1038\/nm1477","article-title":"Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia","volume":"12","author":"Simmons","year":"2006","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.coi.2010.06.003","article-title":"Host response to influenza virus: Protection versus immunopathology","volume":"22","author":"Peiris","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_57","first-page":"320","article-title":"Emergence and dissemination of clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus","volume":"42","author":"Claes","year":"2023","journal-title":"Rev. Sci. Tech."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"a038489","DOI":"10.1101\/cshperspect.a038489","article-title":"The ecology and evolution of influenza viruses","volume":"10","author":"Wille","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/440435a","article-title":"Avian flu: Influenza virus receptors in the human airway","volume":"440","author":"Shinya","year":"2006","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1126\/science.1124513","article-title":"Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus","volume":"312","author":"Stevens","year":"2006","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/viro.1994.1615","article-title":"Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates","volume":"205","author":"Connor","year":"1994","journal-title":"Virology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3201\/eid1506.090072","article-title":"Past, present, and possible future human infection with influenza virus A subtype H7","volume":"15","author":"Belser","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature10831","article-title":"Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA\/H1N1 virus in ferrets","volume":"486","author":"Imai","year":"2012","journal-title":"Nature"},{"key":"ref_64","first-page":"158","article-title":"The pig as a mixing vessel for influenza viruses: Human and veterinary implications","volume":"3","author":"Ma","year":"2008","journal-title":"J. Mol. Genet. Med."},{"key":"ref_65","first-page":"447","article-title":"Novel influenza A viruses in pigs, cattle, and other livestock species: A One Health perspective on cross-species transmission and pandemic risk","volume":"11","author":"Kuchipudi","year":"2023","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36839","DOI":"10.1038\/srep36839","article-title":"Ecological dynamics of influenza A viruses: Cross-species transmission and global migration","volume":"6","author":"Ren","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1038\/s41467-024-48475-y","article-title":"Risk assessment of a highly pathogenic H5N1 influenza virus from mink","volume":"15","author":"Restori","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"786","DOI":"10.3201\/eid2904.221538","article-title":"Outbreak of highly pathogenic avian influenza H5N1 in New England seals","volume":"29","author":"Puryear","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cell.2014.02.040","article-title":"Identification, characterization, and natural selection of mutations driving airborne transmission of A\/H5N1 virus","volume":"158","author":"Linster","year":"2014","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41579-018-0115-z","article-title":"Host and viral determinants of influenza A virus species specificity","volume":"17","author":"Long","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.3201\/eid2212.160450","article-title":"Effect of live poultry market interventions on influenza A(H7N9) virus, Guangdong, China","volume":"22","author":"Wu","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.15585\/mmwr.mm7036a2","article-title":"Using wastewater surveillance data to support the COVID-19 response United States, 2020\u20132021","volume":"70","author":"Kirby","year":"2021","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_73","unstructured":"World Health Organization Global Influenza Strategy 2019\u20132030."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.immuni.2017.09.007","article-title":"The pathway to a universal influenza vaccine","volume":"47","author":"Paules","year":"2017","journal-title":"Immunity"},{"key":"ref_75","unstructured":"US Department of Health and Human Services (2017). HHS Influenza Pandemic Plan."},{"key":"ref_76","unstructured":"Moderna, Inc. (2024). Moderna Awarded $176 Million to Accelerate Development of mRNA-Based Avian Influenza Vaccine, Moderna, Inc."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.ymthe.2020.04.018","article-title":"A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice","volume":"28","author":"Freyn","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_78","first-page":"1","article-title":"Influenza virus-like particles as pandemic vaccines","volume":"433","author":"Pushko","year":"2021","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrd4529","article-title":"Advances in the development of influenza virus vaccines","volume":"14","author":"Krammer","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2155072","DOI":"10.1080\/22221751.2022.2155072","article-title":"Alarming situation of emerging H5 and H7 avian influenza and effective control strategies","volume":"12","author":"Shi","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1600-065X.2008.00668.x","article-title":"Strategies and challenges for eliciting immunity against avian influenza virus in birds","volume":"225","author":"Swayne","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_82","first-page":"e00588-18","article-title":"INSaFLU: An automated open web-based bioinformatics suite for next-generation sequencing data analysis of influenza viruses","volume":"56","author":"Borges","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_83","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\u2014From vision to reality","volume":"22","author":"Shu","year":"2017","journal-title":"Eurosurveillance"},{"key":"ref_84","unstructured":"World Health Organization Tool for Influenza Pandemic Risk Assessment (TIPRA)."},{"key":"ref_85","first-page":"295","article-title":"In silico vaccine prediction: A pipeline for identifying candidate vaccine antigens","volume":"2410","author":"Klingen","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Prosser, D.J., Hungerford, L.L., Erwin, R.M., Ottinger, M.A., Takekawa, J.Y., and Ellis, E.C. (2013). Mapping avian influenza transmission risk at the interface of domestic poultry and wild birds. Front. Public Health, 1.","DOI":"10.3389\/fpubh.2013.00028"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.coviro.2016.11.006","article-title":"Drivers of airborne human-to-human pathogen transmission","volume":"22","author":"Herfst","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"965","DOI":"10.3201\/eid2406.172114","article-title":"Ferrets as models for influenza virus transmission studies and pandemic risk assessments","volume":"24","author":"Belser","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrg.2017.88","article-title":"Towards a genomics-informed, real-time, global pathogen surveillance system","volume":"19","author":"Gardy","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_90","unstructured":"CDC (Centers for Disease Control and Prevention) (2025). Technical Report: Multi-State Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Virus in Dairy Cattle and Reported Human Cases."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.34133\/research.1104","article-title":"Protective Efficacy of a Hemagglutinin-Based mRNA Vaccine Against H5N1 Influenza Virus Challenge in Lactating Dairy Cows","volume":"9","author":"Kong","year":"2026","journal-title":"Research"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:52:19Z","timestamp":1775058739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":91,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["v18040410"],"URL":"https:\/\/doi.org\/10.3390\/v18040410","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]}}}