#Genetic modification of primary #airway epithelial cell cultures defines MX1 as a #barrier for zoonotic #influenza A viruses in the #human respiratory epithelium

 

Abstract

The antiviral innate immune response is a major species barrier that emerging viruses must overcome to infect and transmit efficiently in new hosts. In humans, the interferon-stimulated MX1 gene encodes the antiviral MX1 protein, which restricts zoonotic influenza A viruses (IAVs). Resistance to MX1 is considered a key feature of human-adapted IAVs and a potential determinant of zoonotic and pandemic risk. However, MX1-mediated restriction and viral escape have mostly been investigated in cell lines and animal models, which incompletely recapitulate virus-host interactions in the human airway epithelium, representing the primary site of IAV replication. Although primary human airway epithelial cell (hAEC) cultures, such as airway organoids and air-liquid interface (ALI) cultures, provide a physiologically relevant model, their use in studying MX1 restriction has been limited by challenges in achieving efficient and reliable genetic modification. Here, we used engineered virus-like particles (eVLPs) to deliver Cas9-sgRNA ribonucleoprotein complexes into primary hAECs and disrupt MX1 expression. This approach generated MX1-knockout airway organoids and organoid-derived hAEC ALI cultures with >90% genomic-level editing efficiency and near-complete loss of MX1 protein, while preserving epithelial differentiation at the air-liquid interface. MX1 knockout in hAEC ALI cultures had only a minor effect on the replication kinetics of the human-adapted H1N1pdm09 strain. By contrast, MX1 knockout markedly impaired interferon lambda-mediated restriction of the zoonotic bovine H5N1/Texas and avian H7N9/Anhui strains, resulting in viral titers up to 3-4 logs TCID50 higher than in MX1-competent cultures. These findings provide direct evidence that MX1 restricts zoonotic IAVs in primary human airway epithelium. Our study establishes a biologically relevant platform for assessing the sensitivity of emerging IAVs to a key antiviral host factor and thereby informs evaluations into their zoonotic and pandemic risk.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Swiss National Science Foundation, https://ror.org/00yjd3n13, 310030_207675

Source: 

Link: https://doi.org/10.64898/2026.10.19.759965

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

 

{Extract}

(...)

    {England} 

    Commercial, 32k bird laying flock (73 weeks of age). 

    Positive test for HPAI H5N1, clinical signs presented prior to testing.

(...)

Source:  

Link: https://wahis.woah.org/#/in-review/7918

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

 

{Extract}

(...)

    {Durres Region} 

    As a part pf the surveillance programme implemented in high risk areas, sample were collected from {backyard reared} ducks and geese, none of the which exhibited clinical signs. 

    The reference lab confirmed the presence of the H5N1 virus. 

    All the necessary measures have been implemented on farm in accordance with the CP and in line with the commission delegated regulation 2020/687.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7917

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Avian #Influenza #Report - October 11 - 17 '26 (Wk 42) (HK CHP, Oct. 20 '26): 1 New Human Case of #H5N1 Virus in the #US; 2 New #H9N2 Virus Cases in #China

 

{Excerpts}

(...)

Avian influenza A(H5N1)

    ° {USA} Washington:

        § The patient is currently isolating at home and has not experienced severe illness or required hospitalisation.

        § The case had exposure to dairy cattle infected with avian influenza A(H5N1) virus at a local dairy farm.

        § The Washington state recorded their first detection of avian influenza  A(H5N1) in two dairy farms on October 8, 2026.

Avian influenza A(H9N2)

    °{China} Guizhou Province:

        § A four-year-old boy with onset on September 20, 2026.

    ° Henan Province:

        § A 68-year-old man with onset on September 17, 2026.

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk42.pdf

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The #Risk of an #H5N1 #Influenza #Pandemic

 

Abstract

The last 110 years have seen four influenza A pandemics, where viruses have emerged from mammals or birds with the ability to transmit and cause disease in human populations. Since 2021, a high-pathogenicity strain of avian influenza, H5N1, has caused a panzootic (pandemic of animals), with global spread in wild birds, resulting in frequent spillovers into farmed poultry and into mammals, including mammal species not previously known to be affected by influenza A. This has created increased opportunity for reassortment, mutation, human infection, and potential adaptation to transmit. The risk to humans and the impact are difficult to quantify but of mounting concern to public health bodies. Here, we examine the risk of an H5N1 pandemic emerging and spreading in humans and the potential impact of an H5N1 pandemic.

Source: 

Link: https://doi.org/10.1146/annurev-med-042525-092552

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#USA, #Washington State: Avian #Influenza - Current #Situation and Data (Dept. of Health, Oct. 16 '26): One New Human Case

 

{Excerpts}

Current Situation

    There are several strains of bird flu that wild birds carry worldwide. The most widely circulating, or common, strain in the United States today is H5N1. This strain was first detected in the U.S. in wild birds in January 2022. 

    In Washington state, H5N1 was first identified in a backyard flock in May 2022. 

    H5N1 was first detected in dairy cattle in Washington in October 2026.

    H5N1 has since spread to domestic birds, including commercial poultry and backyard flocks, and to mammals, such as wild and domestic cats, and dairy cattle.

    The first human H5N1 case in Washington state was identified in October 2024 and was linked to close contact with birds and their environment during a commercial poultry outbreak. 

    In 2025, Washington also reported a human infection with H5N5, a strain not previously seen in humans. 

    Other subtypes that have infected humans are H6, H7, H9, and H10. CDC’s Avian Influenza Type A as more information on influenza virus subtypes.

Human Bird Flu Cases in Washington State Residents

{Click on Image to Enlarge}

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(...)

Source: 

Link: https://doh.wa.gov/you-and-your-family/illness-and-disease-z/bird-flu/current-situation-and-data

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#USA, #H5 Avian #Influenza: Current Situation (US CDC, Oct. 16 '26): One New Human Case Reported in #Washington State

 

{Extract}

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National situation summary since 2024

    ° Person-to-person spread: None

        § There is no known person-to-person spread at this time.

    ° Current public health risk: Low

        § The current public health risk is Low.

    ° Human Cases in the U.S.: 72 cases {+1}

    ° Deaths in U.S.: 2 deaths {0}

(...)

Source: 

Link: https://www.cdc.gov/bird-flu/situation-summary/index.html#human-cases

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#USA, #Washington State: #Yakima County Resident Tests Positive for Avian #Influenza { #H5N1 } (Dept. of Health, Oct. 16 '26)

 

{Excerpts}

    Yakima, WA- The Yakima Health District (YHD), in coordination with the  Washington State Department of Health (DOH), is reporting a confirmed case of  avian influenza in a Yakima County resident who was exposed to infected dairy cattle at a Yakima County dairy. 

    The resident has not experienced severe illness or been hospitalized. 

    The individual is isolating at home.

    The risk of avian influenza infection to the general public remains low. 

    People at greater risk include dairy workers and others who have close or  prolonged contact with infected animals or environments contaminated with the  virus. 

    Transmission of avian influenza between humans is extremely rare and has never been documented in the United States. 

    To ensure that human-to-human spread is not occurring, public health officials are contacting anyone who has been in close contact with the patient to monitor for symptoms.

    Since the initial detection of Highly Pathogenic Avian Influenza (HPAI) H5N1 in Yakima County, YHD has been in contact with the impacted dairies to  protect the health of people who may be exposed to infected cattle.

    YHD continues to coordinate with state and federal public health partners to  provide guidance and resources to help protect exposed individuals. This  includes providing tests for exposed individuals who develop symptoms to support  prompt diagnosis and appropriate medical care. 

    YHD is working with partners to connect affected dairies with appropriate  personal protective equipment (PPE) for their workers

(...)

Source: 

Link: https://www.yakimacounty.us/2417/Media-Releases#docaccess-9da5cc1738194b3305738e318406f325

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Mice immunized with #N1 NA in a single cycle infectious virus or in a recombinant nanoparticle #vaccine are protected against lethal challenge with HPAI #H5N1 influenza

 

Abstract

The recent spillover of highly pathogenic (HP) H5N1 clade 2.3.4.4b into dairy cattle and other mammalian species has been concerning. Vaccine candidates that can be rapidly synthesized and implemented are key countermeasures for protecting the human population against emerging pathogens. Here we examine the use of a pH1N1 virus lacking the genetic material for hemagglutinin (HA), limiting the infection to a single cycle (sciIAV) or Cobalt lipid-porphyrin nanoparticles decorated with neuraminidase (NA) of HPAI H5N1 (N1-CoPoP) as vaccine candidates. C57BL/6 mice that were inoculated intranasally with a single dose of pH1N1 sciIAV did not differ in serum NA antibody compared to uninoculated mice. However, mice that were inoculated intramuscularly with the N1-CoPoP alone or in combination with pH1N1 sciIAV had increased N1 IgG antibodies. Upon lethal challenge with HPAIV H5N1, all mice inoculated with either pH1N1 sciIAV or N1-CoPoP were protected from weight loss, unlike unvaccinated mice with substantial body weight losses that succumb to viral infection between 7 and 10 days post infection (dpi). Both pH1N1 sciIAV and N1-CoPoP immunization minimized viral infection such that only one mouse receiving pH1N1 sciIAV had detectable viral titer in the lungs at 4 dpi. By 6 dpi, no mouse inoculated with pH1N1 sciIAV and/or N1-CoPoP had detectable virus in nasal turbinates, lungs or the brain, unlike the high viral titers found in uninoculated mice. Both pH1N1 sciIAV and N1-CoPoP were protective and should be investigated further as alternative vaccine candidates.

Competing Interest Statement

J.F.L. holds interest in POP Biotechnologies. Other authors declare no competing interests.

Funder Information Declared

American Lung Association, https://ror.org/01p3rh655

Texas Biomedical Research Institute

Douglass Foundation

Source: 

Link:  https://doi.org/10.64898/2026.10.11.758125

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

 

{Click on Image to Enlarge}

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By caroline legg - This image has been extracted from another file, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=151715256

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{Extract}

(...)

A wild Eurasian buzzard (common buzzard) in the Južno-Banatski Region.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7899

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#Evidence of Exposure to Highly Pathogenic Avian #Influenza #H5 Viruses in East #Greenland Polar #Bears

 

Abstract

We detected influenza A virus antibodies in plasma collected from East Greenland polar bears during subsistence hunts in 2024 (3/14 [21%]) and 2025 (6/14 [43%]). Four bears from 2025 had antibodies for the globally emerging highly pathogenic avian influenza virus H5 clade 2.3.4.4b, consistent with survival after exposure.

Source: 

Link: https://doi.org/10.3201/eid3211.261050

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

 

{Extracts}

(...)

{Piura Region. Laying hen farm with a total flock of 5,800 birds}

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

    ° It has identified an outbreak of highly pathogenic avian influenza in poultry (laying hens), which exhibited 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 epidemiological unit was cleaned and disinfected; in addition, surveillance around the outbreak was conducted to detect possible cases.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7894

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#Antiviral Susceptibility of Clade 2.3.4.4b #H5N1 and #H5N5 #Influenza Viruses Detected in #Birds in #Russia During 2021–2022

 

Abstract

In this study, we aimed to analyze the antiviral susceptibility of clade 2.3.4.4b H5N1 and H5N5 influenza viruses detected in Russia during 2021–2022. During this period, we investigated 40 avian influenza outbreaks in wild and domestic birds, isolating 109 H5N1 and 9 H5N5 strains. Using a genetic approach, we analyzed the presence of markers associated with reduced susceptibility to baloxavir and M2 blockers, as well as markers of reduced inhibition by neuraminidase inhibitors (NAIs). Additionally, the isolated strains were tested in a functional assay to evaluate the inhibitory activity of oseltamivir, zanamivir, and peramivir against viral neuraminidase. None of the isolates harbored genetic markers of reduced susceptibility to M2 blockers and baloxavir or reduced inhibition by NAIs. Functional assay showed that the median IC50 values of oseltamivir, zanamivir, and peramivir were 1.73, 0.49, and 0.16 nM for the H5N1 subtype, and 0.65, 1.13, and 0.12 nM for the H5N5 subtype, respectively. None of the tested strains demonstrated a ≥10-fold increase in NAI IC50 values compared to the corresponding subtype medians, and were thus classified as having a normal level of inhibition. The median IC50 values of the NAIs determined for the tested avian viruses were comparable to those of a susceptible seasonal A(H1N1)pdm09 strain, except for a slight reduction in oseltamivir activity against H5N1 viruses (4.3-fold) and zanamivir activity against H5N5 viruses (3.4-fold). Our study revealed a group of H5N1 viruses whose NA belonged to the ea5.1 genetic subclade, characterized by NA-Y253H and T452I amino acid substitutions, which exhibited a 28.8-fold decrease in oseltamivir IC50 values compared to the subtype median. These strains were detected in the European and Ural regions of Russia between May 2022 and January 2023, with no subsequent detections in the available surveillance data. To the best of our knowledge, such strains have not been identified outside Russia.

Source: 

Link: https://doi.org/10.3390/v18101126

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

{Excerpts}

(...)

{Vlaanderen Region} 

    ° The birds in the infected aviary have been euthanized (Somateria mollissima, Anas bernieri, Lophodytes cucullatus, Mergellus albellus, brasiliensis brasiliensis, Spatula hottentota, Anas melleri, Aix galericulata) . 

    ° The other birds have not been culled but are being monitored (derogation from Regulation 2020/687, Article 13.2.d) 05/10/2026 

    ° Birds in other aviaries (ibises and geese) were showing symptoms and tested positive for the H5N1 virus. It was therefore decided to euthanise all the animals.

    ° The captive birds in the two infected aviaries were euthanized, as were the three hens in an uninfected aviary. 

    ° The other birds were not culled but are being monitored (derogation from Regulation 2020/687, Article 13.2.d: animals of high genetic, cultural or educational value, duly justified). ; 

    ° PRIMARY OUTBREAK (Tongeren: secondary outbreak linked to the purchase of ducks in Balen)

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7868

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The #mammalian-adaptive #PB2-E627K substitution preserves viral fitness of clade 2.3.4.4b #H5N1 HPAIV in #birds

 

Abstract

Since emerging in 2020, clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has disseminated globally, causing substantial infection and mortality in wild birds and poultry. Additionally, numerous spill-over events into mammals have occurred, including mass mortalities and sporadic human infections. Such events can drive the acquisition of mammalian-adaptive mutations, which further increase the risk to humans; the most well characterised mutation is the glutamate to lysine change at amino acid position 627 in the polymerase basic 2 protein (PB2-627K). Across avian influenza viruses, PB2-627K enhances polymerase activity and replication in mammalian cells, increasing zoonotic and pandemic potential. However, bioinformatic analyses indicate that PB2-627K remains rare among clade 2.3.4.4b H5N1 viruses circulating in avian populations. Here, we investigated the impact of PB2-627K on viral fitness in avian hosts to assess the potential for mammalian-adapted viruses to re-establish in birds, mimicking infection of avian species following scavenging on mammalian species where PB2-627K has already emerged. Using a representative H5N1 virus (European genotype AB), PB2-627K increased polymerase activity and replication in human cells without compromising replication in avian cells. A mammalian-derived PB2-627K H5N1 isolate from a fox exhibited comparable replication kinetics and transmission efficiency in chickens and ducks to a closely related PB2-627E virus. Notably, PB2-627K remained genetically stable at consensus level following infection and transmission in both avian hosts. These findings demonstrate that mammalian-adaptive mutations acquired during spill-over can be maintained in avian populations, potentially elevating zoonotic risk and underscoring the importance of surveillance for such mutations in birds.

Source: 

Link: https://doi.org/10.64898/2026.10.06.757006

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

 

{Excerpt}

(...)

A wild Greylag Goose in Nicosia Region.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7864

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

 

{Excerpt}

(...)

A backyard poultry farm in Araucanía Region.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7872

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

{Extract}

(...)

{Otdar Mean Chey} 

    On 20 September 2026, an outbreak investigation team visited a backyard poultry farm following reports of illness and mortality suspected to be caused by Avian Influenza (AI). 

    A total of three chicken and one duck samples were collected and submitted to NAHPRI/GDAHP for testing of Avian Influenza (H5N1). 

    And On 23 September 2026, laboratory results confirmed that all four samples tested positive for Avian Influenza (H5N1). 

    Additionally, in the same area, one human case of Avian Influenza (H5N1) was confirmed by the Ministry of Health on 27 September 2026.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7875

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#Antibodies targeting a conserved cryptic epitope at the #influenza hemagglutinin head-stem interface via distinct binding modes

 

Abstract

Influenza A virus continues to pose pandemic threats, as demonstrated by the recent global spread of highly pathogenic H5N1 strains. Consequently, the development and characterization of vaccines targeting zoonotic influenza subtypes have become a major focus of the field. In this study, we characterize two broadly reactive antibodies previously isolated from H5N1 vaccinees. Although they have distinct immunoglobulin germline gene usage and binding modes, cryo-EM analysis shows that both antibodies share a highly conserved cryptic epitope at the interface of the hemagglutinin (HA) head and stem domains. The antigenicity of this epitope is influenced by natural amino acid variation at residue 293 of HA subunit 1, and its access is facilitated by acid-induced conformational change of HA. Nevertheless, both antibodies are non-neutralizing and possess only marginal protective efficacy against seasonal and H5N1 viruses in vivo, thus representing suboptimal vaccine responses. Overall, our findings expand the interactions of cross-reactive antibodies with an under-characterized HA epitope and provide insights for next-generation influenza vaccine design.

Competing Interest Statement

N.C.W. consults for HeliXon. All authors declare no other competing interests.

Funder Information Declared

Research Grants Council of the Hong Kong Special Administrative Region, China, HKU C7053-24G

Health and Medical Research Fund, no. 24230352

NIH/NIGMS, GM158411

Vallee Scholars Program

Source: 

Link: https://doi.org/10.64898/2026.09.24.754278

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Establishment of an avian #influenza #surveillance program in #Australia's largest #river basin

 

Abstract

To-date Australia has had mostly coastal occurrences in a small but growing number of species of high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b. The potential impacts of expected spread are the focus of significant preparation activities. Here we report on early surveillance undertaken in 2025-26 in the Murray-Darling Basin, Australia's largest river system, which contains internationally important wetlands that support large multi-species aggregations of waterbirds vulnerable to mass mortality. We detected two low pathogenicity avian influenza (LPAI) viruses of Australian origin in wild waterbirds. Ongoing surveillance will aid in early detection and rapid response in the case of a major inland outbreak of H5N1.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Department of Climate Change, Energy, the Environment and Water

Source: 

Link: https://doi.org/10.64898/2026.09.09.750291

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