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Avian Influenza Viruses: Global Panzootic, Host Range Expansion and Emerging One-Health Threats
by
, , and
Luigi Bruno
1,*, 
Maria Anna Nappo
1,
Raffaele Frontoso
2,*,
Salvatore Montinaro
3,
Rosanna Di Lecce
4,
Chiara Guarnieri
4,
Luca Ferrari
4,*
and
Attilio Corradi
4
1
Department of Prevention, Azienda Sanitaria Locale (A.S.L.) Napoli 3 Sud, Castellammare di Stabia, 80053 Naples, Italy
2
Istituto Zooprofilattico Sperimentale del Mezzogiorno (I.Z.S.M.), Portici, 80055 Naples, Italy
3
Azienda Socio-Sanitaria Locale (A.S.L.), 07100 Sassari, Italy
4
Department of Veterinary Science, University of Parma, 43126 Parma, Italy
*
Authors to whom correspondence should be addressed.
Vet. Sci. 2026, 13(1), 67; https://doi.org/10.3390/vetsci13010067
Submission received: 18 November 2025
/
Revised: 30 December 2025
/
Accepted: 6 January 2026
/
Published: 9 January 2026
Simple Summary
The global spread of highly pathogenic avian influenza viruses (HPAIVs) is a major One-Health concern. HPAIVs infect a wide range of hosts, including wild birds, poultry, marine and semi-aquatic mammals, amphibians, fish, companion animals and equids. Recently, the H5N1 clade 2.3.4.4b virus has shown tropism for mammary epithelial cells in lactating dairy cattle, and the virions showed the ability to spread in raw milk. Climate change, wildlife–livestock interfaces and intensive farming may favor viral persistence and genomic reassortment. Coordinated action, grounded in national and international sanitary regulations and integrating surveillance, vaccination, biosecurity and environmental monitoring, is strategic and essential to limit further host adaptation as well as panzootic and pandemic risks.
Abstract
The review deals with the current knowledge on the global panzootic spread of highly pathogenic avian influenza viruses (HPAIVs), with an emphasis on the H5N1 clade 2.3.4.4b virus. It describes the viral structure, replication, pathotypes and molecular determinants of host range, including sialic-acid receptor usage and key genetic mammalian-adaptation markers (PB2-E627K and PB2-D701N mutations). The host spectrum nowadays extends from wild waterfowl and poultry including seabirds, terrestrial and marine mammals and, based largely on experimental studies or molecular detection, reptiles, amphibians, and fish. Recently, the H5N1 clade 2.3.4.4b virus has shown marked tropism for lactating mammary epithelium in dairy cattle, with virions shed in raw milk. The review reports epidemiology, geographical expansion, clinical presentation, pathogenesis and pathology, diagnosis, immune responses and vaccination approaches across species. It also analyses European Union (EU) and Italian regulatory frameworks, surveillance strategies and biosecurity measures from a One-Health perspective. The review highlights how climate change, wildlife–livestock interfaces, intensive farming and global trade favor viral persistence and genomic reassortment and concludes by stressing strategic actions to limit further host adaptation and panzootic/pandemic risks.
