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H5N1 Influenza Viruses
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H5N1 Influenza Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 6658

Special Issue Editor

Dr. Daniel R. Perez

E-Mail Website
Guest Editor
Poultry Diagnostic and Research Center, Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Interests: influenza viruses; emerging viruses; interspecies transmission of viral pathogens; virus entry and replication; virus host-range; virus ecology and evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global emergence and rapid spread of highly pathogenic avian influenza (HPAI) H5N1 virus has raised significant concerns for both animal and human health, necessitating a comprehensive understanding of this evolving threat. This Special Issue aims to provide a platform for disseminating cutting-edge research on H5N1, covering a wide range of critical topics. We encourage submissions that delve into the intricate virology of H5N1, exploring its genetic diversity, mutations, and the molecular mechanisms underlying its virulence and transmissibility. Epidemiological investigations are crucial to elucidate the complex transmission dynamics of H5N1, including spillover events from avian populations, geographic spread, and risk factors associated with human infection. 

Furthermore, we seek contributions that investigate the pathogenesis of H5N1 infection in diverse hosts, examining the immune responses elicited, the factors influencing disease severity, and the potential for zoonotic transmission. We are particularly interested in studies that address the development of effective vaccines and antiviral therapies, as well as innovative strategies for prevention and control. This Special Issue will serve as a valuable resource for researchers, public health officials, and policymakers working to mitigate the impact of H5N1 on global health and well-being.

Dr. Daniel R. Perez
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • H5N1
  • avian influenza
  • genetic diversity
  • immune response
  • vaccines and antiviral therapies

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Published Papers (6 papers)

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Research

10 pages, 3437 KiB  
Article
Phylogenetic and Mutation Analysis of Hemagglutinin Gene from Highly Pathogenic Avian Influenza Virus H5 Clade 2.3.4.4b in South America
by Alfredo Bruno, Domenica de Mora, Miguel Angel Garcia-Bereguiain and Juan Cristina
Viruses 2025, 17(7), 924; https://doi.org/10.3390/v17070924 (registering DOI) - 28 Jun 2025
Viewed by 148
Abstract
The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America. The introduction of the virus into South [...] Read more.
The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America. The introduction of the virus into South America was reported for the first time in Colombia in October 2022, followed by outbreaks in other South American countries affecting poultry, wild birds, mammals, and humans. In this study, a phylogenetic and mutation analysis of the hemagglutinin (HA) gene of HPAIV H5N1 2.3.4.4b viruses isolated in South America was performed to analyze its evolution and its transmission and zoonotic potential. The analysis shows an increase in the viral effective population size between April and June 2022, which was followed by multiple outbreaks of HPAIV H5N1 clade 2.3.4.4b in South America. Moreover, the virus variants evolved from a recent common ancestor estimated to have existed in June 2017. The mean rate of evolution of the HA gene was 6.95 × 10−3 substitutions per site per year, and the sequence analysis of HA identified a mutation (D171N) located at antibody binding sites and viral oligomerization interfaces, with implications for immune response evasion and new host species infection. Additionally, viral strains from South America share the substitutions L104M, T156A, P181S, and V210A, compared to the vaccine strain A/chicken/Ghana/AVL763/2021. Understanding the dynamics of viral evolution and transmission is essential for effective prevention strategies to mitigate future outbreaks. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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12 pages, 570 KiB  
Article
The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023
by Anna Golke, Tomasz Dzieciątkowski, Olga Szaluś-Jordanow, Michał Czopowicz, Lucjan Witkowski, Monika Żychska, Ewa Domańska, Dawid Jańczak, Tomasz Nalbert, Stephanie Lesceu, Marzena Paszkowska, Justyna Giergielewicz and Tadeusz Frymus
Viruses 2025, 17(6), 855; https://doi.org/10.3390/v17060855 - 16 Jun 2025
Viewed by 786
Abstract
Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional [...] Read more.
Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional epidemiological study to assess the seroprevalence of IAV, especially H5Nx, infections in domestic cats. Eight hundred thirty-five serum samples collected in June 2023 were tested using a competitive ELISA for antibodies to IAV nucleoprotein. Positive or doubtful samples were further screened for H5-specific antibodies. The overall seropositivity for IAV was 8.5% (CI 95%: 6.8%, 10.6%; 71/835 cats), and 23/68 IAV-seropositive cats (33.8%) were also seropositive for H5 antigen. Multivariable analysis identified young age (≤8 years) and male sex as significant risk factors for H5 seropositivity, while non-H5-IAV seropositivity was more common in cats aged ≥12 years. These findings suggest different exposure pathways and host risk profiles for H5 and non-H5 IAVs and underscore the importance of enhanced surveillance in cats, particularly in regions affected by HPAI outbreaks. Given the susceptibility of cats to both avian and human IAVs, including subclinical infections, there is a theoretical risk for viral reassortment. Preventive measures, including vaccinating humans and restricting outdoor access for cats, should be considered in endemic areas. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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23 pages, 1939 KiB  
Article
Phylogenetic Analysis and Spread of HPAI H5N1 in Middle Eastern Countries Based on Hemagglutinin and Neuraminidase Gene Sequences
by Laith N. AL-Eitan, Diana L. Almahdawi and Iliya Y. Khair
Viruses 2025, 17(5), 734; https://doi.org/10.3390/v17050734 - 20 May 2025
Viewed by 715
Abstract
Highly pathogenic avian influenza (HPAI) A/H5N1 viruses threaten animal and human health worldwide. The first documented cases in the Middle East were reported in 2005; however, despite extensive phylogenetic studies, there is limited information on the transmission dynamics of the virus within this [...] Read more.
Highly pathogenic avian influenza (HPAI) A/H5N1 viruses threaten animal and human health worldwide. The first documented cases in the Middle East were reported in 2005; however, despite extensive phylogenetic studies, there is limited information on the transmission dynamics of the virus within this region. We analyzed HA and NA gene sequences from various hosts to address this gap and to understand the virus’s spread and evolution in the Middle East. We hypothesized that H5N1 transmission exhibits host-specific or geographically influenced clade structures in this region. This study traced transmission pathways of HPAI A/H5N1 through a phylogenetic and amino acid sequence analysis of HA and NA gene segments from isolates across different hosts in Middle Eastern countries, using the MUSCLE algorithm for alignments and MEGA11 software for phylogenetic analysis. Sequences were selected from NCBI’s virus database based on geographic and host diversity, including those from birds, humans, and other mammals, and were collected at different time points, predominantly after the early 2000s. An amino acid phylogenetic tree was also constructed to examine the conservation of key HA and NA protein residues, identifying distinct clades linked to specific countries and host species, suggesting a possible interspecies transmission and cross-border spread distinct between Egypt and neighboring countries. These findings underscore the role of migratory birds in regional transmission and point to the need for more targeted surveillance and biosecurity efforts, offering more genomic insights into the spread of HPAI A/H5N1 and contributing valuable information for future prevention strategies. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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13 pages, 1494 KiB  
Article
Dose-Dependent Effect of DNA Vaccine pVAX-H5 Encoding a Modified Hemagglutinin of Influenza A (H5N8) and Its Cross-Reactivity Against A (H5N1) Influenza Viruses of Clade 2.3.4.4b
by Andrey P. Rudometov, Victoria R. Litvinova, Andrei S. Gudymo, Ksenia I. Ivanova, Nadezhda B. Rudometova, Denis N. Kisakov, Mariya B. Borgoyakova, Lyubov A. Kisakova, Vladimir A. Yakovlev, Elena V. Tigeeva, Danil I. Vahitov, Kristina P. Makarova, Natalia P. Kolosova, Tatiana N. Ilyicheva, Vasiliy Yu. Marchenko, Artemiy A. Sergeev, Larisa I. Karpenko and Alexander A. Ilyichev
Viruses 2025, 17(3), 330; https://doi.org/10.3390/v17030330 - 27 Feb 2025
Viewed by 856
Abstract
Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b viruses are widespread in wild and domestic birds, causing severe economic damage to the global poultry industry. Moreover, viruses of this clade are known to cause infections in mammals, posing a potential pandemic threat. Due [...] Read more.
Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b viruses are widespread in wild and domestic birds, causing severe economic damage to the global poultry industry. Moreover, viruses of this clade are known to cause infections in mammals, posing a potential pandemic threat. Due to the ongoing evolution and change in the dominant strains of H5 clade 2.3.4.4b, it is important to investigate the cross-reactivity of vaccines in use and under development against clade 2.3.4.4b viruses. In this study, the immunogenicity of the previously developed DNA vaccine encoding a modified hemagglutinin of the influenza A/turkey/Stavropol/320-01/2020 (H5N8) virus, administered by jet injection at doses of 1, 10, 50, 100, and 200 μg, was investigated. The highest titer of specific to recombinant hemagglutinin antibodies was detected in the group of animals injected with 100 µg of DNA vaccine. The cross-reactivity study of sera of animals immunized with 100 µg of DNA vaccine in a microneutralization assay against the strains A/chicken/Astrakhan/321-05/2020 (H5N8), A/chicken/Komi/24-4V/2023 (H5N1), and A/chicken/Khabarovsk/24-1V/2022 (H5N1) showed the formation of cross-neutralizing antibodies. Moreover, the study of protective properties showed that the DNA vaccine protected animals from mortality after infection with A/chicken/Khabarovsk/24-1V/2022 (H5N1) virus. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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13 pages, 1460 KiB  
Article
Risk Assessment of Spread of the Influenza A Virus in Cows in South Bulgaria
by Gabriela Goujgoulova and Koycho Koev
Viruses 2025, 17(2), 246; https://doi.org/10.3390/v17020246 - 11 Feb 2025
Viewed by 927
Abstract
In this article, we present an assessment of the risk of the potential introduction and spread of highly pathogenic avian influenza (HPAI) in cows in Bulgaria. In the spring of 2024, we witnessed an unprecedented spread of the virus in dairy herds in [...] Read more.
In this article, we present an assessment of the risk of the potential introduction and spread of highly pathogenic avian influenza (HPAI) in cows in Bulgaria. In the spring of 2024, we witnessed an unprecedented spread of the virus in dairy herds in the USA. This crossing of interspecies barriers by the virus creates a real danger of pandemic manifestations in humans. The continued spread of H5N1 clade 2.3.4.4b in dairy populations and other mammalian species and efficient animal-to-animal transmission increases the risk of infection and subsequent spread of the virus in human populations. According to registers, as of 1 November 2022, a total of 559,544 cattle were bred in Bulgaria. The total number of dairy cows decreased by 5.2% year-on-year to 197,996. Farms breeding dairy cows as of 1 November 2022 were 12,439, which is 22.1% less than the previous year. The production of cow’s milk in 2022 amounted to 748,278 thousand liters. Traditionally, the largest share in the total yield of cow’s milk is occupied by the south-central region with 25.9%, followed by the southeastern region with 18.5%. Due to potential risk factors such as the high concentration of dairy cows in high-risk areas for avian influenza A, the possibility of HPAI jumping the interspecies barrier and spreading in dairy herds in Bulgaria is very high. We therefore set out to assess the risk of virus penetration in these herds. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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12 pages, 1328 KiB  
Article
Highly Pathogenic Avian Influenza Contributes to the Population Decline of the Peregrine Falcon (Falco peregrinus) in The Netherlands
by Valentina Caliendo, Beatriz Bellido Martin, Ron A. M. Fouchier, Hans Verdaat, Marc Engelsma, Nancy Beerens and Roy Slaterus
Viruses 2025, 17(1), 24; https://doi.org/10.3390/v17010024 - 27 Dec 2024
Cited by 1 | Viewed by 2538
Abstract
Highly pathogenic avian influenza (HPAI) epizootics have caused repeated mass mortality events among wild birds. The effect of the infection is potentially detrimental for a variety of bird species, including the Peregrine Falcon (Falco peregrinus). The numbers of wintering and breeding [...] Read more.
Highly pathogenic avian influenza (HPAI) epizootics have caused repeated mass mortality events among wild birds. The effect of the infection is potentially detrimental for a variety of bird species, including the Peregrine Falcon (Falco peregrinus). The numbers of wintering and breeding Peregrine Falcons in the Netherlands have recently declined. We investigated the changes in population trends in relation to HPAI H5 virus outbreaks. For this purpose, we analyzed variations in annual numbers of wintering and breeding birds, the virology of reported dead birds, and the presence of the HPAI H5 virus in unhatched eggs. We showed that significant mortalities of Peregrine Falcons had occurred in 2016–2017 and 2020–2023, years of major HPAI H5 virus outbreaks. In particular, the highest rates of bird mortality and HPAI virus infection were reported in 2023. In this year, over 80% (28/32) of the tested birds were positive for HPAI H5 virus. No HPAI H5 virus was present in the eggs. Based on these findings, we concluded that HPAI represents a serious threat to the Peregrine Falcon population in the Netherlands, and, in combination with anthropogenic factors, may contribute to the decline of this species. Targeted HPAI surveillance and disease mitigation measures are necessary for the conservation of this species. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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