Characterization of #H5N1 high pathogenicity avian #influenza virus belonging to clade 2.3.4.4b isolated from Ezo red #fox in #Japan in a mouse model

 

ABSTRACT

H5N1 high pathogenicity avian influenza virus (HPAIV) has spread in wild birds and poultry worldwide. H5N1 HPAIV belonging to the currently predominant clade 2.3.4.4b has infected not only birds but also mammals (wild and domestic animals), with several human infections also being reported, raising concerns for public health. In 2022, a clade 2.3.4.4b H5N1 HPAIV strain, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), was isolated from an Ezo red fox (Vulpes vulpes schrencki) in Hokkaido, Japan; this was the first reported case of clade 2.3.4.4b H5N1 HPAIV isolation from a mammalian species in Japan. Several amino acid substitutions in the PB2 protein play an important role in the adaptation of avian influenza viruses to mammals, but Fox/Hok/1/22 PB2 does not have any of these well-known mammalian-adapting PB2 substitutions. Here, we investigated the biological properties of Fox/Hok/1/22 in a mouse model and found that this virus was highly virulent in mice and replicated well in multiple organs, including the lungs and brain. We then examined whether viruses isolated from these organs acquired known mammalian-adapting PB2 amino acid substitutions, such as PB2 E627K. Deep sequencing analysis of viral RNA from mouse brain and lungs revealed that virus with PB2-627E was predominant in three of four mice, whereas the PB2-627K substitution was predominant in one mouse. These results indicate that Fox/Hok/1/22 is highly virulent in mice despite lacking known PB2 substitutions involved in mammalian adaptation.

IMPORTANCE

The H5N1 avian influenza virus has caused severe disease in birds worldwide and is now spreading to mammals, including humans. In 2022, this virus was detected for the first time in an Ezo red fox in Japan. To understand its potential impact on mammals, we studied this virus in mice and found that it caused severe illness, spreading to multiple organs, including the lungs and brain. Surprisingly, despite lacking genetic mutations typically associated with mammalian adaptation, the virus was highly virulent in mice. This finding suggests that the H5N1 virus may pose a greater threat to mammals, including humans, than previously thought. Given their continued spread among wild and domestic animals, our findings underscore the urgent need to monitor how recent H5N1 viruses behave in mammals.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01097-25

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Decoding non-human #mammalian adaptive #signatures of 2.3.4.4b #H5N1 to assess its #human adaptive potential

ABSTRACT

The 2.3.4.4b clade highly pathogenic avian influenza H5N1 infected diverse non-human mammalian species, gained mammal-to-mammal transmission potential, and caused sporadic human infections. However, whether non-human mammals enable the human adaptation of 2.3.4.4b H5N1 to establish human infections is unclear. Gain-of-function research restrictions may hinder the assessment of 2.3.4.4b H5N1 human adaptations. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human-adapting mutations, which are identical to the residues of H1N1pdm09 and seasonal human H3N2 viruses, while showing a few species-specific adaptations that might be potential barriers for successful human infections. The polymerase complex proteins, PA and PB2, acquired human adaptations in non-human mammals, with fox-infected viruses showing more positive selection in the polymerase complex. The human-adapting Q591K/R substitution in PB2 appeared only in the 2.3.4.4b clade but not in previously circulating H5N1 strains. Despite minimal changes in hemagglutinin (HA), A160T and T199I mutations near the receptor binding site of HA in dairy cattle viruses indicate the rapid HA glycan surface evolution affecting virus entry and immune evasion. The unbiased quantitative assessment of virus adaptations indicated that 2.3.4.4b H5N1 circulating in bears, cattle, dolphins, and foxes might show better human adaptive potential. Thus, 2.3.4.4b H5N1 appears to be acquiring human adaptations due to natural selection pressure in non-human mammals. Overall, our study delineates human adaptation and infection risk of specific non-human mammalian circulating 2.3.4.4b H5N1 strains.

IMPORTANCE

The 2.3.4.4b clade H5N1 virus emerged as a panzootic strain, leading to the unprecedented deaths of domestic and wild birds and diverse non-human mammalian species. Intriguingly, the 2.3.4.4b H5N1 transmitted to diverse mammalian species and gained mammal-to-mammal transmission, suggesting its pandemic potential. The H5N1 outbreaks in dairy cattle and sea lions are devastating, and they contributed to sporadic human infections. This indicates the ability of non-human mammal hosts, like dairy cattle, as potential sources for human transmission. However, the signatures of non-human mammal adaptations of 2.3.4.4b H5N1 and how these adaptations drive the human adaptive potential of 2.3.4.4b H5N1 are unclear. In this study, we show the specific molecular patterns of H5N1 proteins that determine species-specific adaptations in non-human mammals. We identified that 2.3.4.4b H5N1 circulating in non-human mammals is rapidly evolving with critical adaptations in PA, PB2, and HA and gaining human adaptive potential in specific non-human mammalian species.

Source: Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.00948-25

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Avian #Influenza in #Ireland: A Spatiotemporal, Subtype, and Host-Based Analysis (1983-2024)

Abstract

Avian influenza virus (AIV) is a significant global concern, causing widespread mortality in wild birds, domestic poultry and most recently wild and domestic mammals. This study presents a retrospective analysis of AIV detections in the Republic of Ireland. Data was sourced from official surveillance databases, peer-reviewed literature and grey literature sources. Spatio-temporal, host-specific and subtype patterns were assessed using descriptive statistics, chi-square tests, linear regression and kernel density estimations. A total of 2,888 confirmed AIV detections were recorded from 25 of Ireland's 26 counties. Wild birds accounted for 98.7% of detections, with domestic birds comprising 1.3% and two detections in foxes. H5N1 was the most prevalent subtype (96.7%) followed by H5N8 and H6N1. Spatial clustering was observed in urban areas, particularly Dublin. The highest seasonal peak occurred during summer, contrasting with traditional winter-associated patterns. Several detections occurred in migratory species outside of typical residency periods, suggesting potential climate-related shifts in migration behaviour. This study represents the first review of AIV surveillance data in Ireland to date. The findings highlight evolving patterns in virus distribution, seasonality and host dynamics, with implications for national surveillance strategies. Continued cross-species monitoring and integration of ecological data are essential to inform effective management strategies.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.26.656175v1

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#Norway - #Influenza A #H5N5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A Red Fox in Tromso Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6450

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#Germany - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

One red fox in Sachsen and one in Nordrhein-Westfalen States.

Source: WOAH, https://wahis.woah.org/#/in-review/6398

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#Belgium - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Follow up report 8

Two wild cats, two European Polecats, Forty-four Domestic Mustelidae, Twenty-two foxes in various Regions.

Source: WOAH, https://wahis.woah.org/#/in-review/4971?reportId=172740&fromPage=event-dashboard-url

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#Surveillance of Highly Pathogenic Avian #Influenza Virus in Wild #Canids from #Pennsylvania, #USA

Abstract

The avian influenza virus is a global pathogen with significant health and economic implications. While primarily a pathogen of wild and domestic birds, recent outbreaks of the H5N1 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b have caused mortality in a wide variety of mammals, including members of the Canidae family, on multiple continents. Despite sporadic mortality events globally, the epidemiology and pathobiology of H5N1 HPAIV in wild canids remains poorly defined. During 2022–2024, 41 wild canid carcasses (diagnostic cases), including 23 red foxes and 18 gray foxes, were tested for the influenza A virus (IAV) via PCR, with five red fox kits testing positive (12%). Infected animals had variably severe encephalitis, pneumonia, and occasionally myocarditis associated with strong immunolabeling for IAV. Serum from 269 wild canids in Pennsylvania was tested for antibodies to IAV, including 133 samples collected prior to 2021 (pre-H5N1 HPAIV 2.3.4.4b introduction) and 136 collected after 2022 (post-H5N1 HPAIV 2.3.4.4b introduction). All samples collected prior to 2021 were seronegative for IAV. Two coyotes from 2024 were seropositive for IAV but were negative for antibodies to the H5 and N1 subtypes. Collectively, these data suggest that while sporadic H5N1 HPAIV infection and mortality can occur in wild canids, particularly juvenile red foxes, infection was limited in these outwardly healthy and opportunistically sampled animals. Future studies should utilize a risk-based approach to target sampling of wild canids at increased risk for H5N1 HPAIV infection, such as those around waterfowl habitats or spatially around wild bird or domestic animal outbreaks.

Source: Animals, https://www.mdpi.com/2076-2615/14/24/3700

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Highly Pathogenic Avian #Influenza (HPAI) #H5N1 virus in #Finland in 2021-2023 – Genetic diversity of the viruses and infection kinetics in #human dendritic cells

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 is known for its virulence and zoonotic potential, infecting birds and mammals, thus raising public health concerns. Since 2021 its spread among birds has led to cross-species transmission causing epizootics among mammals, eventually impacting fur animal farms in Finland in 2023. To analyze the infectivity of the Finnish H5N1 isolates in human cells, representatives of diverse H5N1 isolates were selected based on the genetic differences, host animal species, and the year of occurrence. The infection kinetics of the selected H5N1 isolates from wild pheasant and fox, and fur animals blue fox and white mink were examined in human monocyte-derived dendritic cells (moDCs) with H5N1 human isolate as a control. Although the isolate from pheasant (a wild bird) showed weakly reduced replication and viral protein expression in human cells compared to mammalian isolates, no discernible differences in virus replication in moDCs was observed. This study revealed similar infectivity in human moDCs for all five H5N1 isolates, regardless of the observed genetic differences. While H5N1 human infections remain rare, the virus poses a risk for widespread epizootics in mammals such as fur animal farms and, more recently, dairy cattle.

Source: Emerging Microbes & Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2447618

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#Slovenia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild red fox in Podravska Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6119

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