Emerging and Re-Emerging Avian Influenza Viruses in Wildlife

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 2305

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Independent Researcher, Atlanta, GA, USA
Interests: host–pathogen interactions; avian diseases; avian influenza virus; conservation research; high-throughput sequencing
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Special Issue Information

Dear Colleagues,

Avian influenza viruses (AIVs) remain a significant threat to wildlife, domestic animals, and human health. As members of the Orthomyxoviridae family, AIVs are categorized by their hemagglutinin (HA) and neuraminidase (NA) subtypes. Wild birds, particularly waterfowl, serve as the natural reservoirs of these viruses and play a vital role in their ecology—facilitating viral evolution, reassortment, and global transmission.

In recent years, outbreaks of highly pathogenic avian influenza viruses (HPAIV), notably H5N1 clade 2.3.4.4, have increasingly affected not only avian populations but also a wide range of mammalian hosts. Over 43 mammalian species across Europe, North America, South America, and Asia have been impacted by spillover events. In some cases—especially among marine mammals—these infections have been severe and fatal. Alarmingly, 2024 marked the first reported cases of efficient cow-to-cow and cow-to-human transmission of HPAIV, a pattern not previously observed in the A/goose/Guangdong (GsGD) lineage.

This Special Issue aims to highlight recent advances and emerging insights in the biology, evolution, and ecology of avian influenza viruses in wildlife. We welcome original research and review articles focused on, but not limited to, the following topics:

  • Surveillance and epidemiology of AIVs in wild birds and mammals;
  • Genomic and phylogenetic studies on AIV evolution;
  • Impact of AIVs on wildlife populations and conservation;
  • Spillover risk and interspecies transmission dynamics;
  • Climate change effects on AIV distribution and migratory pathways;
  • Wildlife management and control strategies;
  • Novel diagnostic, modeling, and predictive tools;
  • Application of high-throughput sequencing in virus detection and characterization.

We encourage submissions from the fields of virology, immunology, evolutionary biology, ecology, and public health. Studies incorporating novel methodologies and interdisciplinary approaches are especially welcome. We look forward to your valuable contributions to this important collection.

Dr. Klaudia Chrzastek
Guest Editor

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Keywords

  • avian influenza virus
  • HPAIV
  • LPAIV
  • wildlife
  • surveillance
  • epidemiology
  • phylogenetics
  • next-generation sequencing

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Published Papers (2 papers)

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Research

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19 pages, 9012 KB  
Article
Comprehensive Evolutionary and Structural Analysis of the H5N1 Clade 2.4.3.4b Influenza a Virus Based on the Sequences and Data Mining of the Hemagglutinin, Nucleoprotein and Neuraminidase Genes Across Multiple Hosts
by Kalpana Singh, Yashpal S. Malik and Maged Gomaa Hemida
Pathogens 2025, 14(9), 864; https://doi.org/10.3390/pathogens14090864 - 31 Aug 2025
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Abstract
H5N1 Influenza A virus continues to pose a significant zoonotic threat, with increasing evidence of interspecies transmission and genetic adaptation. Previous studies primarily focused on avian or human isolates, with limited comprehensive analysis of H5N1 evolution across multiple mammalian hosts. Existing molecular surveillance [...] Read more.
H5N1 Influenza A virus continues to pose a significant zoonotic threat, with increasing evidence of interspecies transmission and genetic adaptation. Previous studies primarily focused on avian or human isolates, with limited comprehensive analysis of H5N1 evolution across multiple mammalian hosts. Existing molecular surveillance often lags behind viral evolution; this study underscores the necessity for real-time monitoring of ongoing mutations affecting pathogenicity and transmissibility. Our goals are (1) to retrieve and analyze HA, NP and NA gene sequences of H5N1 Influenza A virus from diverse hosts, including humans, poultry and multiple mammalian species, to assess genetic diversity and evolutionary patterns and (2) to evaluate positive selection sites across the three major genes (HA, NP and NA) to determine adaptive mutations linked to host adaptation and viral survival. To achieve these goals, in this study, we considered (78 HA), (62 NP) and (61 NA) gene sequences from diverse hosts, including humans, poultry and multiple mammalian species, retrieved from the NCBI database. Phylogenetic analysis revealed distinct clade formations, indicating regional spread and cross-species transmission events, particularly from avian sources to mammals and humans. Selection pressure analysis identified positive selection across all three genes, suggesting adaptive mutations contributing to host adaptation and viral survival. Homology modeling and molecular dynamics simulations were performed to generate high-quality structural models of HA, NP and NA proteins, which were subsequently validated using multiple stereochemical parameters. Domain analysis confirmed conserved functional motifs, while protein–ligand docking demonstrated stable interactions at conserved binding sites, despite observed residue substitutions in recent isolates. Earlier research concentrated on HA alone; this study integrates HA, NP and NA genes for a broader understanding of viral evolution and adaptation. These findings highlight ongoing evolutionary changes in H5N1 genes that may enhance viral adaptability and pathogenicity, underscoring the need for continuous molecular surveillance and updated antiviral strategies. Full article
(This article belongs to the Special Issue Emerging and Re-Emerging Avian Influenza Viruses in Wildlife)
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Review

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17 pages, 606 KB  
Review
H5N1 Clade 2.3.4.4b: Evolution, Global Spread, and Host Range Expansion
by Klaudia Chrzastek, Carolin M. Lieber and Richard K. Plemper
Pathogens 2025, 14(9), 929; https://doi.org/10.3390/pathogens14090929 - 15 Sep 2025
Viewed by 1223
Abstract
Highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype pose a continuous threat to animal and public health due to their zoonotic potential, rapid evolution, and ability to spread across continents. Since the emergence of the A/goose/Guangdong/1/96 (GsGD) H5 lineage in 1996, [...] Read more.
Highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype pose a continuous threat to animal and public health due to their zoonotic potential, rapid evolution, and ability to spread across continents. Since the emergence of the A/goose/Guangdong/1/96 (GsGD) H5 lineage in 1996, several clades have caused devastating outbreaks in poultry and wild bird populations, occasionally resulting in human infections. Of the many clades that have evolved, only three—clades 2.2, 2.3.2.1, and most recently 2.3.4.4b—have demonstrated the ability to spread globally. The 2.3.4.4b clade has raised significant concern due to its continuous geographic expansion, establishment in new ecosystems, including Antarctica, and increasing reports of mammalian infections, including companion animals, marine mammals, and livestock. Recently, cow-to-cow and cow-to-human transmission marked a paradigm shift in the epidemiology of avian influenza and emphasized the need for continued surveillance. This review summarizes the historical emergence, global spread, and molecular evolution of H5 HPAIVs with a specific focus on the recent expansion of clade 2.3.4.4b and its capacity for mammalian spillover. Full article
(This article belongs to the Special Issue Emerging and Re-Emerging Avian Influenza Viruses in Wildlife)
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