#H5N1 #influenza binding and cell entry via #human class II #MHC, and blocking by cross-reactive #antibodies

 

Abstract

Highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses are currently responsible for a multi-species outbreak affecting wild birds, poultry, numerous mammalian species, and humans. Influenza A viruses typically initiate infection through binding to sialic acid, although select bat and human influenza viruses can also exploit class II major histocompatibility complex (MHC–II) molecules for cell entry. Here we show that emerging H5N1 clade 2.3.4.4b viruses, but not historical H5 lineages, bind human MHC–II HLA-DR and mediate sialic acid-independent cell entry. Hemagglutinin binding to primary human immune cells varies with MHC–II expression and is further shaped by HLA–DR allelic variation, identifying host genetic determinants that may influence susceptibility to infection. Mammalian-adaptive substitutions within the hemagglutinin sialic acid receptor-binding domain reduce MHC–II binding, suggesting this interaction is remodeled during clade 2.3.4.4b H5 adaptation to a human host. Lastly, cross-reactive monoclonal antibodies isolated from clade 2.3.4.4b H5–naive humans can block the hemagglutinin–MHC–II interaction. These findings identify a previously unrecognized receptor pathway in contemporary H5N1 viruses and reveal that both human genetic variation and pre-existing humoral immunity can modulate this interaction, with implications for host range, cellular tropism, spillover risk, and therapeutic intervention.

Competing Interest Statement

S.D.B. has consulted for Regeneron, Sanofi, Novartis, Genentech, Pfizer, Visterra, and Otsuka on topics unrelated to the research presented here; owns stock in AbCellera Biologics; and is a scientific cofounder of Immunera, Inc.; S.E.H reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck.

Funder Information Declared

NIH/NIAID CEIRR contract, 75N93021C00015

NIH, 1U54CA260517

HIPC, U19AI057266

P01 grant, 5P01AI153559

David Crown Foundation endowment

Early Postdoc Mobility Fellowship Stipend from the Swiss

National Institutes of Health NRSA T32, T32OD011121

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.22.739677v1

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Mapping Reported Modes of #Transmission of Highly Pathogenic Avian #Influenza #H5N1 to #Humans: A Scoping Review

 

Abstract

Background

Highly Pathogenic Avian Influenza A (subtype H5N1) poses a threat to human health, and its pandemic potential emphasizes the need to better understand detailed reported transmission pathways to humans. Existing literature is outdated or lacks detailed, comprehensive analysis of the range of transmission routes and how the virus may enter the human body.

Objective

To comprehensively map all reported H5N1 transmission pathways to humans, as well as viral entry routes.

Methods

CINAHL, Embase, MEDLINE, Scopus, PubMed, grey literature, and reference lists (of included studies) were searched up to October 29th, 2025, with no language restrictions. Observational studies and grey literature reporting H5N1 transmission evidence to humans were included. Two reviewers conducted duplicate screening independently (two of three reviewers per record). One reviewer completed data extraction, which was cross-verified for accuracy by a second. Findings were summarized narratively.

Results

120 sources met inclusion criteria (70 studies, 50 grey literature). Reported H5N1 transmission pathways were classified into animal-to-human (109 of 120 sources, 90.8%; including poultry-to-human in 100 sources [83.3%] and cattle-to-human in nine sources [7.5%]), environment-to-human (32 of 120 sources, 26.7%), and human-to-human (14 of 120 sources, 11.7%). Reported transmission pathways were further classified as direct or indirect contact, synthesized, and linked to suspected routes of human entry, including mucosal entry (eyes, nose, mouth), inhalation of aerosols or droplets, ingestion, and percutaneous exposure. Entry routes are biologically plausible and do not imply relative likelihood or causal attribution.

Conclusions

There are multiple reported pathways of H5N1 exposure, and a single pathway may involve multiple ways to infect humans. Further research is needed to determine causal mechanisms, identify specific risk factors and measures of association, and strengthen evidence-based prevention strategies.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S235277142600176X?via%3Dihub

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

 

{Click on Image to Enlarge}

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By Manuel González Olaechea y Franco - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12026471

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These occurrences were detected through passive surveillance conducted by the Ministry of Environment and Energy along the entire coast of mainland Ecuador.

{Peruvian Pelican} Wild bird population in situ in Guayas Province (bird morbidity history). Out of eight birds, one tested positive.

Source: 

Link: https://wahis.woah.org/#/in-review/7717

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#Oseltamivir #Resistance in #Human #Influenza #H5N1 and #H7N9 Infections: A Mini Review

 

Abstract

Avian influenza viruses (AIVs) have been reported to cause infections in humans following avian-to-human transmission, resulting in a range of clinical outcomes. A(H5N1) and A(H7N9) infections, which constitute the majority of human AIV cases, are responsible for severe infections leading to high mortality. The neuraminidase inhibitor oseltamivir is expected to play a major role for the control of AIV infections in humans. However, the emergence of resistance may compromise the impact of antiviral therapy. The objective of this article is to review human cases of A(H5N1) and A(H7N9) infections for which mutations of oseltamivir resistance were detected. Neuraminidase mutations rapidly occurred in a subtype-specific manner, with H274Y and N294S substitutions predominating in A(H5N1) cases and the R292K substitution in A(H7N9) cases. Serious clinical outcomes and mortality were seen in most A(H5N1) and A(H7N9) cases despite oseltamivir therapy, thus highlighting the need for improving antiviral strategies against these AIVs.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag393/8722865

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#Geographic Concentration of #Genomic #Surveillance for Highly Pathogenic Avian #Influenza #H5, South #Asia, 2015-2025

 

Abstract

Early detection of mammalian adaptation in highly pathogenic avian influenza A(H5) depends on genomic surveillance, yet its distribution across high-burden regions is poorly characterized. We quantified open-access (GenBank/INSDC) H5 genomic coverage relative to reported outbreak burden across nine South Asian countries during 2015-2025, linking isolates to FAO EMPRES-i/WOAH events. Of 919 H5 isolates, 814 (89%) came from one country (Bangladesh); the other eight contributed 105. India, with the largest burden (322 events), yielded only 42 isolates (13 per 100); Nepal, 2 of 78; Afghanistan, none of 5. Concentration was extreme (Gini 0.83) and unchanged by adding restricted GISAID records (1,297 combined isolates; Bangladesh 89%) or by normalizing to poultry or human population. Because reported outbreaks track reporting effort, these coverage ratios are directional, not rates. This single-country dependency, deepest where burden is highest, is a regional early-warning vulnerability.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.07.20.26358505v1

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Within- and between-host #dynamics of highly pathogenic avian #influenza in domestic #birds from #Pennsylvania #farms and live bird #markets

 

Abstract

Since late 2021, highly pathogenic avian influenza viruses (HPAI) of the H5 subtype clade 2.3.4.4b have spread across the Americas, devastating wildlife, agricultural animals, and resulting in dozens of human spillovers. National surveillance strategies generally provide only a single representative sequence per poultry outbreak, precluding fine-scale geographic transmission inference or studies of within-outbreak evolution. We produced high-quality deep sequence data from 46 infected Galliformes and Anseriformes sampled from commercial farm and live bird market (LBM) outbreaks in Pennsylvania from 2023-2025. We found that H5N1 viruses were introduced into Pennsylvania at least 68 independent times. We recover independent origins of live bird market outbreaks within the same county 3 weeks apart, and transmission between Pennsylvania LBM and New York commercial birds, suggesting high transmission risk within the Northeast live bird market distribution system. Analyses of within-farm variant populations show frequent variant sharing between samples from the same outbreak, suggesting that variants are propagated among epidemiologically linked infections. We identified 9 known adaptive mutations in these samples, including one instance of PB2 D701N in a LBM chicken sample, suggesting that while rare, concerning mammalian adaptive mutations can be present within these domestic outbreaks. Our data suggest that domestic bird outbreaks support high circulating diversity and wide transmission bottlenecks, increasing the risk of minority variants arising and propagating between infections. These data can help inform targeted biosecurity measures and better quantify the risk of viral adaptation during agricultural outbreaks.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIAID, NIH 75N93021C00015

Pew Charitable Trusts

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.17.739193v1

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Elicitation of #stem-directed #antibodies in rhesus #macaques by a conventional #hemagglutinin immunogen

 

Abstract

Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIH NIAID, Division of Microbiology and Infectious Diseases, P01-AI089618

NIH NIAID Division of AIDS, Center for HIV/AIDS Vaccine Immunology, U19-AI067854

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.16.738984v1

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#Togo - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

Poultry farms in the Maritime Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7714

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Detection of #H5N1 HPAIV Clade 2.3.4.4b Avian #Influenza Virus in Backyard #Chickens in #CostaRica

 

Abstract

Influenza A virus is a segmented, negative-sense RNA virus. Since the early 2020s, H5 clade 2.3.4.4b viruses have spread widely across Europe, Africa, and Asia, affecting wild birds and poultry. Costa Rica reported its first H5 clade 2.3.4.4b avian influenza virus (AIV) case on 19 January 2023. This study describes an outbreak in backyard chickens and ducks. Initial serum samples collected on 24 January showed three chickens negative for AIV, while one duck tested positive by ELISA and agar gel immunodiffusion (AGID). During a second visit on 27 January, three of four chicken sera collected tested positive by ELISA and AGID. Tissue samples were positive for influenza A by qRT-PCR. Next-generation sequencing recovered five of the eight viral genomic segments, and the hemagglutinin cleavage site sequence (REKRRKR↓G) confirmed a highly pathogenic avian influenza virus (HPAIV) H5 strain. The samples were submitted to the National Veterinary Services Laboratories for confirmation. Serological testing showed reactivity to North American low pathogenic H5 antigens, and qRT-PCR amplified influenza A and N1 genes. Virus isolation and next-generation sequencing (NGS) of all eight viral genome segments were successfully performed at the WHO Collaborating Centre at St. Jude Children’s Research Hospital (SJCRH).

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/799

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#Bovine-derived #H5N1 #influenza virus efficiently infects lactating #swine via the #mammary gland

 

Abstract

Since 2024, highly pathogenic influenza A(H5N1) viruses have spread extensively among U.S. dairy cattle, where they replicate efficiently in the mammary gland and are shed at high titers in milk. To directly assess susceptibility of commercial swine populations to bovine-derived H5N1 virus, lactating sows with prior influenza virus vaccination histories representative of U.S. commercial swine production systems were inoculated via the intramammary route and co-housed with their 1-week-old piglets to evaluate disease outcomes, viral replication, and potential for vertical transmission. Intramammary inoculation of lactating sows resulted in sustained viral RNA shedding in milk, while piglets exhibited sporadic oral viral RNA positivity that mirrored viral kinetics in milk. Lesions in mammary tissue and viral antigen staining, as well as development of neutralizing antibody responses and changes in milk color and consistency, further confirmed infection in the sows. Despite these molecular findings, none of the animals developed overt clinical disease, and respiratory involvement was not noted during the study period. Collectively, we demonstrate that intramammary exposure results in productive influenza A(H5N1) virus infection in lactating sows despite their vaccination histories, indicating the potential threat of viral spillover into commercial swine populations. The clinically inapparent nature of infection presents a risk of subclinical spread and underscores the importance of expanding viral surveillance to swine.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Swine Health Information Center, 25-020

United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA), 2025-39601-44639

National Institutes of Health, P30 CA016058

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.18.739312v1

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Characterization of #bovine-derived #H5N1 viruses expressing fluorescent and luminescent reporter #proteins

ABSTRACT

Highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses present a broad host range, with recent spillover and sustained transmission in dairy cattle reported in the USA. Replication-competent reporter viruses are critical tools that enable real-time monitoring of virus replication, facilitating high-throughput screens. In this study, we engineered three recombinant H5N1 clade 2.3.4.4b reporter viruses expressing nanoluciferase (NLuc) and two fluorescent reporter proteins, miniGFP2 and UnaG within the open reading frame of the nonstructural gene of the bovine A/Cattle/Texas/063224-24-1/2024 (TX2/24) virus. All reporter viruses replicated efficiently in vitro, presenting replication kinetics comparable to the parental rTX2/24 virus, but exhibited smaller plaque sizes, suggesting reduced cell-to-cell spread. In vivo infection studies in mice showed comparable pathogenicity among all four viruses, although rTX2/24-miniGFP2 and rTX2/24-UnaG exhibited decreased virus shedding relative to rTX2/24 and rTX2/24-NLuc. Virus titrations and in situ localization of virus replication sites demonstrated robust replication in respiratory tissues, with slightly attenuated systemic dissemination of all three reporter viruses. Fluorescent virus neutralization assays using miniGFP2 and UnaG reporter viruses accurately quantified neutralizing antibody titres in sera from naturally infected dairy cattle, consistent with wild-type virus assays. Additionally, the utility of the NLuc reporter virus for antiviral screening was validated against oseltamivir in vitro. Collectively, these results establish the H5N1 TX2/24-based reporter viruses as versatile and biologically relevant tools for investigating H5N1 pathogenesis and for use in serological and antiviral drug screens.

Source: 

Link: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002298

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Pan-continental #spillover #risk: integrated spatiotemporal, transmissibility and #surveillance analysis of avian #influenza #H5N1 in #Africa

 

Abstract

Background: 

The HPAI H5N1 panzootic represents a critical threat to human health in Africa, where traditional poultry systems and dense human-animal interfaces facilitate frequent zoonotic spillover. While sporadic human cases raise pandemic concerns, continent-wide integration of spatial dynamics, transmissibility indicators, and surveillance performance has been lacking. This study quantifies avian influenza transmission over two decades across Africa, identifies geographical hotspots, and evaluates the responsiveness of current surveillance systems.

Methods: 

We analysed 8,037 avian influenza outbreak events and 369 laboratory-confirmed human cases, predominantly caused by HPAI H5N1 (2004–2025), using harmonised data from FAO (EMPRES-i+), WHO, and WOAH. A Bayesian Besag-York-Mollié (BYM) spatiotemporal model estimated residual transmission risks and Incidence Rate Ratios (IRR) by subtype. The basic reproduction number (R₀) was derived via an exponential growth model applied to human outbreak phases across infectious durations of 7–30 days. Surveillance responsiveness was assessed by quantifying notification delays between clinical observation and official reporting.

Results: 

Risk of infection in animals: HPAI H5N1 was the dominant strain, representing 87.8% of animal cases, with Egypt acting as the primary epidemiological epicentre (66% of total records). The spatiotemporal model revealed that H5N1 is associated with a significantly higher risk of animal infection (IRR = 8.37; 95% CI: 6.65–10.53). Although 71% of outbreaks were reported within 5 days of detection, significant delays (≥15 days) occurred in 12% of cases, with notable regional disparities. Risk of infection in human: H5N1 was associated with a 67-fold increase in the incidence of human cases compared to other subtypes (IRR = 66.78; 95% CI: 25.29–176.37). Sensitivity analyses yielded R0 estimates ranging from 1.05 (95% CI: 0.91–1.31) to 1.23 (95% CI: 0.60–2.33), indicating localised epidemic potential.

Conclusion: 

Our findings highlight a persistent and geographically heterogeneous H5N1 reservoir in Africa with high zoonotic affinity. Although sustained human-to-human transmission remains limited, the identification of dual poultry-human hotspots and localised R0 peaks underscores the urgent need for geographically targeted One Health interventions. Strengthening real-time reporting systems and improving biosecurity in high-risk poultry value chains are critical to mitigating future pandemic threats on the continent.

Source: 

Link: https://www.frontiersin.org/journals/epidemiology/articles/10.3389/fepid.2026.1813211/full

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

 

Di Antoine Lamielle, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=128547540

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    ° This is the first detection of highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus in New Zealand. 

    ° The detection is in a single subantarctic skua (Stercorarius antarcticus) found on Petone Beach, Lower Hutt. 

    ° The bird was found weak and emaciated and no neurological or respiratory clinical signs were observed. 

    ° Subantarctic skua are an ocean-going species. 

    ° Genomic sequencing indicates that the virus is closely related to H5N1 HPAI clade 2.3.4.4b viruses recently detected in Western Australia. 

    ° An epidemiological investigation is underway, and general surveillance is continuing. At this time, there is no evidence of further spread. 

    ° Vaccination of specific populations of threatened avian species is being initiated.

    ° A single ocean-going subantarctic skua (Stercorarius antarcticus), also known as brown skua.

Source: 

Link: https://wahis.woah.org/#/in-review/7709

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Detection of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.2 Virus in #Swine after Experimental Inoculation

 

Abstract

Highly pathogenic avian influenza H5NX clade 2.3.4.4b viruses continue to circulate globally. Reintroduction of Eurasian lineage viruses into North America and reassortment with endemic low pathogenicity strains have resulted in new genotypes, including D1.2. To assess pathogenicity and cellular tropism, we intranasally inoculated genotype D1.2 virus into pigs. We isolated virus from nasal secretions from most inoculated animals for multiple days. At 5 days postinoculation, PCR and immunohistochemistry detected virus in musculoskeletal, respiratory, digestive, lymphatic, and nervous systems and isolates from meat juice. At 35 days postinoculation, we detected viral antigen and low levels of RNA in the brain of an animal with lesions consistent with a viral etiology and found viral antigen in the ethmoid of 2 animals. Consistent detection in nasal swab specimens, combined with subclinical respiratory infection, systemic distribution, and protracted detection of clade 2.3.4.4b virus in swine, suggest identifying infection in commercial swine without overt respiratory signs could be difficult.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1765_article

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#Peru - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

    ° The National Agricultural Health Service (SENASA) within its epidemiological surveillance responds to reports of suspected animal diseases. 

    ° It has identified an outbreak of highly pathogenic avian influenza in poultry (fighting birds) exhibiting respiratory and neurological signs. 

    ° Real-time PCR confirmed the presence of the H5N1 avian influenza virus, prompting the immediate implementation of quarantine measures and an epidemiological investigation. 

    ° All birds were culled, and the affected premises were cleaned and disinfected; in addition, surveillance around the outbreak was conducted to detect possible cases.

    ° A premises raising fighting cocks and backyard poultry of various ages

Source: 

Link: https://wahis.woah.org/#/in-review/7700

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About #birdflu and the #risk to #NewZealand {First case of #H5N1 detected in a wild seabird} (Min. Agriculture, July 15 '26)

 

SITUATION UPDATE: 15 July 2026

    A single ocean-going sea bird has tested positive for H5 bird flu in New Zealand.

    The bird was found on Petone Beach in Wellington and reported to our exotic pest and disease hotline. 

    Subsequent testing confirmed H5 bird flu (H5N1 avian influenza clade 2.3.4.4b).

    This is the first detection of H5 bird flu in New Zealand. It hasn't been found in any other birds and there are no detections in poultry.

    The risk to human health remains low.

    New Zealand is well prepared to respond and will react quickly to protect poultry production, and to reduce impacts on wildlife and communities.

        ° Be alert and use good habits to limit the impact of bird flu.

        ° Keep your distance. Stay away from sick or dead wildlife. Keep pets away too.

        ° Keep clean. Wash your hands and clean your gear after being outdoors.

        ° Know when to report. If you see 3 or more sick or dead wildlife, report them to the exotic pest and disease hotline on 0800 809 966.

Source: 

Link: https://www.mpi.govt.nz/biosecurity/pest-and-disease-threats-to-new-zealand/animal-disease-threats-to-new-zealand/high-pathogenicity-avian-influenza/about-avian-influenza-and-the-risk-to-nz

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Avian #Influenza #Report: July 5 – 11 '26 (Wk 28) (HK CHP, July 14, 2026)

{Excerpt}

(...)

Avian influenza A(H5N1) 

    

    ° Phnom Penh {Cambodia}: 

        

        - The case involved a 9-month-old girl.

        - She has been isolated in the hospital and is receiving intensive medical care. 

        - The source of infection has not yet confirmed and the investigation is ongoing. 

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk28.pdf

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Rapid #Expansion of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.1 Virus across #Flyway Regions, North #America, Fall 2024

 

Abstract

Highly pathogenic avian influenza clade 2.3.4.4b virus continues to circulate in North America and has caused severe human disease. That clade includes genotype D1.1, which became dominant in birds in late 2024. Recent phylodynamic reconstructions place D1.1 emergence in mid-2024 but differ on its inferred origin and early dissemination pathways. We combined targeted surveillance of wild birds in Arizona with publicly available US clade 2.3.4.4b hemagglutinin sequences to estimate when D1.1 genotype emerged and to infer its diffusion among the 4 major US flyways. Phylodynamic analyses showed transitions concentrated among adjacent flyways regions, consistent with stepwise dissemination during fall 2024 and limited support for long-distance Pacific–Atlantic exchange. The Pacific Flyway showed patterns consistent with an early source and the Central Flyway with a secondary hub linked to onward spread. Our findings support coordinated genomic surveillance across adjacent flyways to reduce detection delays and improve situational awareness during rapid viral expansion.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0205_article

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Highly Pathogenic Avian #Influenza #H5N1 in South #America, 2022–2025: Spread, Affected Species, and Southward Expansion into the #Antarctic Region

 

Abstract

The H5N1 highly pathogenic avian influenza (HPAI) virus has caused severe global losses, reaching South America in 2022 and Antarctica in 2024. Here, we synthesize outbreak reports submitted to the World Organization for Animal Health by South American countries and overseas territories in this continent, and document the virus’s unprecedented expansion into Antarctica, affecting wild birds, wild mammals, and domestic poultry. Phylogenetic and time-calibrated Bayesian analyses were performed on available genomic sequences. Over 6 million domestic birds were lost, mostly from commercial operations. Of the 11 South American countries and overseas territories that reported H5N1 to WOAH, 10 reported infections in wild birds, spanning 104 species, 59.62% of which are migratory and predominantly non-trans-equatorial. Marine mammal outbreaks followed wild bird detections, with the South American sea lion (Otaria flavescens) being the most reported species. Several Antarctic bird species with migratory behavior were also reported in South America. Genomic analyses revealed multiple introduction events, regional viral diversification, and patterns consistent with repeated cross-species spillover events. These findings highlight H5N1’s extensive ecological reach in the Southern Hemisphere and underscore the urgent need for a One Health approach that strengthens wildlife and backyard-poultry surveillance, alongside coordinated regional action to control and prevent further HPAI spread.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/764

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Isolation and characterization of a clade 2.3.4.4b genotype #D1.1 #H5N1 virus from dairy #cattle in #Wisconsin

 

ABSTRACT

Highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses of clade 2.3.4.4b have recently been detected in U.S. dairy cattle following multiple spillover events from avian reservoirs. In December 2025, HPAI H5N1 virus was identified in a dairy herd in Wisconsin through the National Milk Testing Strategy. Here, we report the isolation of a clade 2.3.4.4b, genotype D1.1 H5N1 virus, A/dairy cow/Wisconsin/25G05743-001/2025 (WI5743-H5N1), from bulk milk associated with the affected herd, describe its phylogenetic relationships, and assess its pathogenicity in mice. Infectious virus was recovered following blind passage in embryonated chicken eggs. Phylogenetic analysis demonstrated that WI5743-H5N1 is distinct from previously reported D1.1 viruses detected in dairy cattle in Nevada and Arizona, supporting an independent introduction into cattle, and indicating a likely local avian source. Compared with closely related avian viruses, WI5743-H5N1 encoded the mammalian-adapting substitution PB2-E627K and additional amino acid differences in HA, PB1-F2, and NS1. In mice, WI5743-H5N1 replicated efficiently in respiratory tissues and was detectable in the brain but exhibited lower lethality relative to other recent clade 2.3.4.4b, genotype B3.13 viruses. Together, these findings highlight the genetic and phenotypic diversity of HPAI H5N1 viruses infecting dairy cattle and underscore the importance of continued surveillance and functional characterization of emerging strains.

IMPORTANCE

Highly pathogenic avian influenza A(H5N1) viruses have recently entered U.S. dairy cattle through multiple spillover events from avian reservoirs, creating new opportunities for viral adaptation in mammals. Here, we describe the isolation and characterization of a clade 2.3.4.4b, genotype D1.1 H5N1 virus from bulk milk collected during a spillover event in Wisconsin in December 2025. Phylogenetic analyses demonstrated that this virus represents an independent introduction into dairy cattle distinct from previously reported D1.1 viruses identified in Nevada and Arizona. Although the virus encoded the mammalian-adapting PB2-E627K substitution, it exhibited comparatively low lethality in mice, highlighting the complexity of mammalian adaptation and pathogenicity in H5N1 viruses. These findings expand current understanding of the genetic and phenotypic diversity of H5N1 viruses infecting dairy cattle and emphasize the importance of continued surveillance and functional characterization of emerging strains.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00761-26

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