Frequent seasonal #reassortment between high and low path #viruses drives the diversification of #influenza #H5N1

 

Abstract

Since 2021, highly pathogenic (HPAI) H5N1 viruses have spread across the Americas, diversifying via reassortment into new genotypes that have spilled into humans and livestock, raising fears of a new influenza pandemic. Pandemic lineages are typically associated with reassortment, but we currently have limited understanding of where and when reassortment is expected to occur, which limits our ability to assess pandemic risks. Using a dataset of 9,052 full-genome sequences, we show that reassortment and novel genotype formation are associated with seasonal variation in low pathogenicity avian influenza (LPAI) cases and with the spatial and host distributions of viral transmission. We pinpoint ducks, geese, and the Central flyway as frequent sources of new genotypes, and show that reassortment rates vary seasonally, driven by mixing between high- and low-pathogenicity viruses. Cattle spillover genotypes (B3.13 and D1.1) evolved during periods of high reassortment, implicating reassortment as a common occurrence in lineages evolving during particular time periods. Together, these findings reframe reassortment as a predictable ecological process, with direct implications for how surveillance and pandemic risk assessment should be designed.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

US Centers for Disease Control Insight Net, CDC-RFA-FT-23-0069

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.17.719307v1

____

#Infection of the #bovine mammary #gland by avian #H5N1 subclade 2.3.4.4b #influenza viruses

 

Abstract

The emergence of the panzootic clade of highly pathogenic avian influenza H5N1 (2.3.4.4b) in 2020 marked a major expansion in the host range of influenza A viruses (IAVs), raising concerns about further cross‑species transmission events and zoonotic spillover. Introduction of 2.3.4.4b viruses into U.S. dairy herds has resulted in widespread circulation, accompanied by reduced milk yield, mastitis, and high viral loads in milk. Notably, virus circulation in dairy cattle represents a novel route for mammalian adaptation and transmission that has already led to more than 40 human cases in the U.S. since 2024. Here, we investigated whether avian clade 2.3.4.4b viruses could infect mammary tissue from Aberdeen Angus, Holstein Friesian, and Limousin cattle, three breeds commonly farmed in Europe, the Americas, and Oceania. Using mammary gland explants, we inoculated tissues with attenuated reassortant viruses expressing the haemagglutinin and neuraminidase glycoproteins of three 2.3.4.4b viruses that predated the emergence of H5N1 in US cattle: A/chicken/England/053052/2021 (AIV07), A/chicken/Scotland/054477/2021 (AIV09), and A/chicken/England/085598/2022 (AIV48). Infected epithelial cells were identified using immunohistochemistry in explants from both the teat and gland cistern for all three breeds following infection with AIV09 and AIV48, indicating that mammary tissue from each of the three tested cattle breeds cattle is permissive to H5N1 infection. Lectin staining showed expression of both α2,3‑linked and α2,6‑linked sialic acids in the mammary tissue of all donors showing that all three breeds have the potential to support infection with both avian-adapted and mammalian adapted IAVs. Together, these findings demonstrate that mammary glands from both beef and dairy cattle breeds are permissive to infection with avian‑adapted and mammalian-adapted H5N1 viruses and highlight the potential for this tissue to act as a mixing vessel for IAV reassortment, underscoring the need to include cattle in ongoing H5N1 surveillance and risk‑assessment frameworks.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MR/Y03368X/1, MC_UU_0034/2, MC_UU_0034/3, MC_UU_0034/1

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/V004697/1

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.16.718897v1

____

#Bovine #H5N1 #influenza viruses have adapted to more efficiently use #receptors abundant in #cattle

 

Abstract

Sustained mammal-to-mammal transmission of high pathogenicity H5N1avian influenza viruses is reshaping the host range of these pathogens. One of the longest-running mammalian transmission chains involves the B3.13 genotype circulating in U.S. dairy cattle which was detected early in 2024. Genomic analysis revealed selection and rapid fixation of haemagglutinin mutations D104G and V147M. We demonstate, via glycomic profiling, that bovine tissues, including the mammary gland, are enriched in N- and O-linked glycans capped with N-glycolylneuraminic acid (NeuGc), a sialic acid absent in humans and birds, which instead express only N-acetylneuraminic acid (NeuAc). Early cattle H5 viruses poorly recognized NeuGc, but D104G and V147M enabled efficient engagement of both NeuAc- and NeuGc-containing receptors. These mutations enhanced replication in bovine mammary tissue without major attenuation of replication in human lung and primary nasal epithelial cells. NeuGc-driven receptor adaptation therefore promotes viral fitness in cattle while potentially limiting immediate zoonotic risk. Deep mutational scanning further identifies alternative haemagglutinin substitutions that confer NeuGc usage and represent surveillance markers for emerging cattle H5 lineages.

Competing Interest Statement

JDB and BD are inventors on Fred Hutch licensed patents related to deep mutational scanning. JDB consults for Pfizer, GSK, Apriori Bio, and Invivyd.

Funder Information Declared

Medical Research Council, MR/Y03368X/1, MR/R010757/1, MC_UU_0034/2, MC_UU_0034/3

BBSRC, BB/Y007298/1, BB/X006123/1, BB/X006166/1, BBS/E/PI/230002A, BBS/E/PI/230002B

BBSRC, BBS/E/PI/23NB0004, BBS/E/PI/23NB0003, UKRI2253, BB/V004697/1

Defra, SE2227

Royal Society, https://ror.org/03wnrjx87, RGS\R2\242118

Houghton Trust, HT/SPRG/23/04

Flanders, G005323N, G051322N, G010326N

CEIRR, 75N93021C00045

The Rockefeller Foundation, PC-2022-POP-005

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.02.715584v1

____

#Tropism and #Replication Competence of #Cattle #Influenza #H5N1 Genotype B3.13 Virus in #Human Bronchus and #Lung Tissue

 

Abstract

In 2024, influenza A(H5N1) genotype B3.13 viruses emerged from cattle and caused mild spillover infections in humans. Using human bronchus and lung tissue, we evaluated tropism, replication, and pathogenesis of 2 cattle influenza isolates. Those viruses showed moderate replication competence and induced robust proinflammatory responses, suggesting potential risk for human health.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1926_article

____

The emergence and molecular #evolution of #H5N1 #influenza viruses in #USA dairy #cattle

 

Abstract

Prior to 2024, highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses circulated predominantly in wild birds and poultry. In 2024 and 2025, 2.3.4.4b genotypes B3.13 and D1.1 were detected in United States dairy cattle. Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. Spillover occurred shortly after the formation of the reassortant genotypes and was followed by months of cryptic transmission prior to detection. We found that both B3.13 and D1.1 evolved at higher rates in cattle relative to birds, primarily due to relaxed purifying selection. Site-specific analyses identified genomic sites under positive selection in cattle relative to birds, indicating adaptation and likely contributing to improved viral fitness after spillover. Intensified genomic surveillance in dairy cattle is essential as population immunity introduces additional selection pressures, with ever-changing risk for human emergence.

Competing Interest Statement

M.A.S. receives contracts from Johnson & Johnson and Gilead Sciences outside the scope of this work. M.U.G.K. received consulting fees from Takeda, Bavaria Nordic, and Google DeepMind for work unrelated to the manuscript.

Funder Information Declared

Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, G051322N, G051323N

UK Medical Research Council/Department for Environment, Food and Rural Affairs (DEFRA) FluTrailMap-One Health consortium, MR/Y03368X/1

Biotechnology and Biological Sciences Research Council (BBSRC)/DEFRA ‘FluTrailMap’ consortium, BB/Y007298/1

Pirbright Institute’s Strategic Program Grants, BBS/E/PI/230002A, BBS/E/PI/230002B

EMBO Installation Grant, 5305

Academy of Medical Sciences Springboard, 1049

Centers of Excellence for Influenza Research and Response, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, 75N93021C00015, 75N93021C00014

National Institutes of Health, AI135995, AI153044, AI192139

Rockefeller Foundation, PC-2022-POP-005

Health AI Programme from Google.org

Oxford Martin School Programmes in Pandemic Genomics & Digital Pandemic Preparedness

European Union's Horizon Europe, 874850, 101086640

Wellcome Trust, 303666/Z/23/Z, 226052/Z/22/Z, 228186/Z/23/Z

United Kingdom Research and Innovation, APP8583

Medical Research Foundation, MRF-RG-ICCH-2022-100069

UK International Development, 301542-403

Bill & Melinda Gates Foundation, INV-063472, INV-090281

Novo Nordisk Foundation, NNF24OC0094346

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.30.713641v1

____

Compartmentalized #cytokine #networks and systemic immune remodeling in #bovine mammary #H5N1 #infection.

 

Abstract

Highly pathogenic avian influenza A H5N1 has recently expanded its mammalian host range; in 2024, genotype B3.13 emerged in U.S. dairy cattle with pronounced mammary tropism. In the past, Influenza A virus immunology has been characterized primarily in respiratory infection models, whereas this study delineates immune responses after intramammary infection. An intramammary H5N1 challenge in Jersey cows in the early dry-off period enabled integration of dose- and compartment-resolved (alveoli versus teat cistern) cytokine and chemokine profiles with peripheral leukocyte dynamics and H5/N1-specific antibody responses. Infection-induced quarter-restricted, monophasic inflammatory networks peaking at 3 to 7 days post-infection, coordinated peripheral myeloid expansion and IFN gamma competent lymphocyte activation, and rising antibody titers across quarters.

Competing Interest Statement

The J.A.R. laboratory received support from Tonix Pharmaceuticals, Xing Technologies, Genus plc and Zoetis, outside of the reported work. J.A.R. is an inventor of patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections, owned by Kansas State University.

Funder Information Declared

Funding for this study was partially provided through grants from the Howard Hughes Medical Institute Emerging Pathogens Initiative (NCW), the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, the BRI Endowed Professorship in Animal Infectious Diseases (JAR), the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases (CEZID) from the National Institute of General Medical Sciences (NIGMS) under award number P20GM130448 (JAR, IM), and the NIAID supported Centers of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016 to JAR).

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.06.710145v1

____

#Dairy Sites with #Milk Exposure Are Most Likely to Have #Detection of #Influenza A Virus

 

Abstract

Highly pathogenic avian influenza virus of the H5N1 subtype has been infecting U.S. dairy cattle and spreading among dairy operations since March 2024. H5N1 surveillance systems for dairies are needed, but information on whether environmental sampling can inform these systems is lacking. To guide a surveillance framework, we determined the environmental sites with Influenza A virus (IAV) detection on H5N1-affected dairies (n = 25) in four states (California, Colorado, Michigan, and Ohio) and explored sample characteristics that may have influenced detection. A total of 581 samples from dairy environmental sites were characterized for IAV RNA via rRT-PCR, and classified into six categories. A total of 94 samples (16.2%) had IAV detected, and the Ct values measured from these samples were typically higher than those measured in bulk tank milk from a subset of sampled herds. A majority of IAV detections were made from the following site categories: milking equipment/personal protective equipment, parlor surfaces, and wastewater/lagoons/manure. These results suggest that environmental sites most likely to be contaminated with IAV on dairies are those with exposure to milk. Meanwhile, mixed effect logistic modeling showed that days into an outbreak that samples were collected was associated with IAV detection. These results provide a framework within which to continue the assessment of environmental sampling as a surveillance tool for dairy H5N1. This framework can be strengthened by studies that perform further IAV viral characterization and collect samples from sites prior to, during, and after H5N1 outbreak periods.

Source: 

Link: https://www.mdpi.com/2076-2607/14/3/584

____

Evaluation of an #H5 #influenza virus #mRNA-lipid nanoparticle (LNP) #vaccine in lactating dairy #cows

 

Abstract

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.

Competing Interest Statement

S.E.H. and D.W. are co-inventors on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins and as a vaccine platform. D.W. is also named on patents describing the use of lipid nanoparticles and lipid compositions for nucleic acid delivery. S.E.H. reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. JDB consults for Apriori Bio, Invivyd, GSK, Pfizer, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to viral deep mutational scanning.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, 75N93021C00015

United States Department of Agriculture, https://ror.org/01na82s61, 5030-32000-231-000-D, 3200-231-112-I

United States Department of Energy, https://ror.org/01bj3aw27, DE-AC05-06OR23100

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709308v1

____

#Pathogenesis of #H5N1 Clade 2.3.4.4b in dry Jersey #cows following intramammary inoculation shows within-host compartmentalization

 

Abstract

Dairy cattle have emerged as a prolific amplifying host for highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b and a new source for cross-species and zoonotic transmission. Independent introductions of H5N1 with unclear exposure routes have been reported in several dairy herds across the U.S. These events escalate the pandemic potential of HPAIV H5N1 as transmission within and between mammalian species present opportunities for mammalian adapted H5N1 viruses to emerge. Although more than 1000 herds have been infected, bovine H5N1 influenza virus pathogenesis, transmission, and evolution in dairy cattle remains not well characterized. Working with H5N1-infected lactating cattle in high containment has been a major challenge due to the required infrastructure and logistics associated with housing, husbandry, and waste management for this model. Thus, developing alternative bovine models that maintain biological relevance while reducing operational complexity is warranted. Here, we evaluate the susceptibility of lactating Jersey cattle in the dry-off period, and characterize the effect of inoculation dose on the mammary pathogenicity of HPAIV H5N1 genotype B3.13. The results of this study demonstrate that dairy cows 21 days into the dry-off period are highly susceptible to HPAIV H5N1, recapitulating the severe clinical and pathological outcomes observed in infected lactating cows under experimental conditions and in field cases. We also observed an association between virus dose and the onset and severity of mastitis in individual udder-quarters and compartmentalized clonal expansion of variant populations. Overall, this study demonstrates that dry cows can provide a feasible model to study H5N1 virology, pathology, and humoral immunology in dairy cows.

Competing Interest Statement

The J.A.R. laboratory received support from Tonix Pharmaceuticals, Genus plc, Xing Technologies and Zoetis outside of the reported work. J.A.R. is inventor on patents and patent applications, owned by Kansas State University, on the use of antivirals and vaccines for the treatment and prevention of virus infections. The other authors declare no competing interests.

Funder Information Declared

This work was supported by the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, the USDA Animal Plant Health Inspection Service’s NBAF Scientist Training Program, the AMP and MCB Cores of the Center on Emerging and Zoonotic Infectious Diseases (CEZID) , and the NIAID supported Centers of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016 and subcontract A21-0702-S001). NIGMS. The sequencing infrastructure used in the study was funded by the USDA Animal Plant Health Inspection Services (AP20VSD&B000C086), while sequencing methodology development was funded in part by the USDA National Institute of Food and Agriculture (NIFA) Agriculture and Food Research Initiative (AFRI) (award no. 2021-68014-33635). H.M.M. was supported in part by NIAID T32055397.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.04.709389v1

____

Primary bovine embryonic #fibroblasts demonstrate variable #fitness following #infection with avian influenza #H5N1 strains and are susceptible to a recently circulating human #H1N1pdm09 strain

 

ABSTRACT

The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions and the limited availability of established cell culture models. Primary bovine embryonic fibroblasts (BeEFs) were isolated and investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles, infectious virus production, viral replication, and plaque morphology in BeEFs following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here demonstrate increased expression of α-2,3 sialic acids compared to α-2,6 sialic acids in BeEFs, similar to sialylation profiles previously reported in bovine mammary tissue. These data also display increased viral fitness of the bovine origin HPAI H5N1 strains across bovine and avian cell lines, consistent with previous characterization in bovine mammary tissue. Furthermore, BeEFs were fully susceptible to a 2022 H1N1pdm09-like IAV strain while maintaining resistance to the 2009 H1N1pdm09 IAV as previously characterized in mammary cells. This study highlights the ongoing zoonotic adaptation of HPAI H5N1 in mammals and the potential for coinfection with select human H1N1 2009 pandemic lineage strains, enabling the potential development of reassortant strains. These data support the ability of BeEFs to serve as a complementary in vitro system for studying IAV infections in bovine hosts.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.03285-25

____

The #bovine mammary #gland as a crucible for zoonotic #influenza virus emergence: Receptor-mediated #adaptation of HPAI #H5N1 clade 2.3.4.4b

 

Abstract

The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species. This review explores the molecular mechanisms underpinning this cross-species transmission, focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors, functions as a novel biological crucible for viral adaptation. Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations—such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans, potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity and that single HA mutations are sufficient to shift binding preference to human receptors. The unprecedented mammalian spread of clade 2.3.4.4b, coupled with its capacity for reassortment and the recent case of a dairy farm worker infection, underscores an urgent zoonotic and pandemic threat. This review contextualizes the outbreak within the fundamental principles of influenza virus receptor biology and viral evolution, highlighting critical knowledge gaps that must be addressed through integrated surveillance and multidisciplinary research. Understanding the interplay between host receptor distribution and viral plasticity in this new niche is paramount for mitigating the risk of a future influenza virus pandemic emerging from the bovine reservoir.

Source: 

Link: https://link.springer.com/article/10.1007/s00705-026-06529-0

____

An #outbreak of highly pathogenic avian #influenza #H5N1 could impact the dairy #cattle sector and the broader #economy in the #USA

 

Abstract

The outbreak of Highly Pathogenic Avian Influenza H5N1 in U.S. dairy cattle poses substantial risks to public health, economic sustainability of farming, and global food systems. Using a Computable General Equilibrium model, we simulate its short- to medium-term impacts on Gross Domestic Product and other macro-economic outcomes for the US and its main trading partners. We simulate impacts under the current situation and realistic and reasonable worst-case scenarios. We estimate domestic economic losses ranging between 0.06% and 0.9% of US GDP, with losses to the dairy sector ranging between 3.4% and 20.6%. Trading partners increase dairy production to compensate for the loss. Current government subsidies are about 1.2% (95% HDI: 1% to 1.4%) of output losses, and likely insufficient to incentivise farmers to step up surveillance and biosecurity for mitigating the possible emergence of H5N1 strains with pandemic potential into human populations.

Source: 

Link: https://www.nature.com/articles/s43247-025-03153-9

____

Protective Efficacy of a #Hemagglutinin-Based #mRNA #Vaccine Against #H5N1 #Influenza Virus Challenge in Lactating Dairy #Cows

 

Abstract

Highly pathogenic avian influenza H5N1 virus has spread to over 1,080 dairy farms across 18 states in the United States, resulting in 41 human infections and posing serious risks to both animal and public health. To address these risks, a hemagglutinin-based mRNA–lipid nanoparticle vaccine was developed, and its safety, immunogenicity, and protective efficacy in high-yielding lactating dairy cows were evaluated. The vaccine was well tolerated, had no adverse effects on health or milk production, and induced strong antibody responses. Two weeks after the second immunization, all the immunized cattle were fully protected against a high-dose H5N1 virus challenge. Notably, two-thirds of the cattle were still completely protected even at the 19th week after the first vaccination, when their serum antibody levels were very low. These data demonstrate that the mRNA vaccine confers robust, lasting protection against H5N1 virus in lactating dairy cows, providing a foundation for clinical trials.

Source: 

Link: https://spj.science.org/doi/10.34133/research.1104

____

Retail #Milk #Monitoring of #Influenza #H5N1 in Dairy #Cattle, #USA, 2024–2025

 

Abstract

US retail milk monitoring during April 13–May 3, 2024, identified influenza A(H5N1) viral RNA in 36% of retail milk samples, indicating widespread undetected infections in US dairy cows. After federal initiatives, reported infections more closely aligned with findings in retail milk during December 27, 2024–January 29, 2025, reflecting improved detection and control.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/2/25-1332_article

____

#Netherlands: #Antibodies to {#H5N1} #birdflu virus found in dairy #cow (Min. Agriculture, Jan. 24 '26)

{Automatic translation from Dutch to English}

Date: January 23, 2026 

Regarding: Dairy cow with antibodies against bird flu 

Dear Chair, Through this letter, I am informing the House, also on behalf of the Minister of Health, Welfare and Sport, about the situation surrounding a dairy cow with antibodies against bird flu (highly pathogenic avian influenza, HPAI). 

No evidence has been found of active virus circulation of bird flu among the dairy cows on this farm in the municipality of Noardeast-Fryslân (province of Friesland). 

There are also no signs of bird flu spreading at other dairy farms. 

I am currently conducting follow-up investigations and have asked all involved parties to be alert to any potential signs. 

Situation: 

The Netherlands Food and Consumer Product Safety Authority (NVWA) received a report on December 24, 2025, about two sick cats. 

One of these cats tested positive for bird flu. 

The cat in question died on December 26, 2025. 

The second cat tested negative and has fully recovered. 

I informed your House of this in my letter of January 13th, including Parliamentary Document 28807, no. 322. 

Following this report, the Netherlands Food and Consumer Product Safety Authority (NVWA) conducted source and contact tracing. 

This revealed a relevant contact with a dairy farm; the cat in question originated from this dairy farm. 

On January 15th, the dairy cattle on this farm were screened. 

Milk samples were taken from several of the cows present, and a sample was also taken from the bulk milk. 

At the time of sampling, no animals showing symptoms of the disease were present on the farm. 

The samples were sent to Wageningen Bioveterinary Research (WBVR) for analysis. 

The results of the PCR tests, which can detect the virus in milk, were negative for both the individual samples and the bulk milk sample. 

This confirmed that no virus was present among the dairy cattle on the farm. 

In addition, the samples were tested for the presence of antibodies. 

On January 20, the WBVR reported that one cow had antibodies to H5N1 avian influenza. 

The presence of antibodies indicates a previous infection with the virus. 

The cow in question had suffered from mastitis and respiratory problems in December. 

These are Symptoms that can be observed in a dairy cow infected with avian influenza. 

At the time of sampling, this cow had recovered. 

Following this positive antibody test, the NVWA (Netherlands Food and Consumer Product Safety Authority) revisited the farm on January 22nd. 

During this visit, blood and milk samples were taken from all cattle present. 

A bulk milk sample was also taken again. 

Today, January 23rd, 2026, the PCR results from these tests were received. 

All but five samples were negative. 

The bulk milk was also PCR negative. 

The five remaining individual milk samples resulted in a test error in the laboratory and will be retested this weekend. 

Based on the PCR results known so far, from last week and today, there is no indication of active circulation of avian influenza virus among the dairy cattle on the farm. 

The five final PCR results will be available this weekend. 

If a positive result is unexpectedly obtained, I will inform Parliament immediately. 

In addition, the results of the antibody testing will follow later next week. 

Antibody testing is important to determine whether more animals have been exposed to the virus, which could indicate past virus circulation. 

Other mammals on the farm (such as dogs, cats, and horses) are currently showing no symptoms. 

Avian influenza in dairy cattle: 

As far as we know, antibodies against avian influenza have not previously been demonstrated in dairy cattle in Europe. 

However, since March 2024, there have been numerous avian influenza outbreaks among dairy cattle in the United States (Parliamentary Document 28807, No. 298). 

The virus causing these outbreaks in dairy cattle in America has not been found in Europe to our knowledge. 

The symptoms exhibited by cows with avian influenza are primarily reduced milk production, fever, loss of appetite, and thick, discolored milk. 

The avian influenza virus is primarily excreted in cows' milk. 

Most dairy cows recover from infection and eventually return to their previous milk production levels. 

It is also possible for a cow infected with avian influenza to show no symptoms; even in that case, the cow often sheds the virus. 

An infected cow sheds infectious virus for about two weeks after infection. 

These symptoms are based on experiences in the US.1 

In response to the large number of avian influenza outbreaks among dairy cows in the US, a policy manual for HPAI in dairy cows2 was developed in early 2025. 

Milk Safety 

Previously, the NVWA's Bureau for Risk Assessment and Research (BuRO) conducted research at the request of the Ministry of Health, Welfare and Sport (VWS) into the management of food and feed safety risks of HPAI virus in milk3. 

In this research It is confirmed that pasteurizing milk completely inactivates the avian influenza virus present. 

The milk is then safe for human consumption and poses no risk to public health or the spread of the virus. 

It is important that raw milk and raw-milk dairy products from cows infected with avian influenza are not consumed. 

Monitoring dairy cattle: 

Individual infection of a dairy cow with the avian influenza virus can occur. 

It is important to know whether this leads to spread within and between farms. 

There are currently no indications that this is the case. 

The basic animal health monitoring program conducts a so-called syndrome surveillance, which involves weekly national and regional monitoring of bulk milk deliveries to determine whether there are any animal health problems in dairy cattle. 

This is a sensitive tool that is particularly valuable when new conditions arise that do not produce specific or noticeable symptoms. 

In addition, the basic monitoring program utilizes pathological examination, and unexplained problems can be reported to the Veekijker (cattle watcher). 

This also makes it possible to identify individual suspected cases of avian influenza infection. 

To date, the basic monitoring has not found any indications that suggest avian influenza infection in dairy cows. 

Naturally, I am closely monitoring the situation and have asked all stakeholders to do so. 

In the short term, I will ask the experts to provide a risk assessment. 

I will also ask experts to analyze possible infection routes and to assess the effectiveness of the monitoring options for HPAI in cattle. 

Furthermore, I have informed stakeholders about this new situation and asked them to report any notable findings. 

Public Health Risk: 

Based on the currently available data, the RIVM (National Institute for Public Health and the Environment) estimates the risk to public health to be very low. 

Because the other cows on the farm also tested negative in the PCR test, it seems unlikely that the virus could have spread from the cow to the other cows. 

Due to the cat that previously tested positive near the farm, individuals working or living on the farm were already known to the Municipal Health Service (GGD). 

These individuals have not shown any symptoms consistent with (avian) influenza since then. 

To be on the safe side, all persons exposed to the cow will still be offered testing for an active or past infection. 

Milk on this farm is used only for pasteurized products, meaning any virus present is inactivated and poses no risk of external contamination. 

Furthermore, the milk from the previously infected cow was not processed for human consumption due to the existing mastitis pattern. 

Therefore, the chance that virus from the infected cow has ended up in the milk for human consumption is very small. 

Given the new situation, the RIVM will soon organize a Zoonosis Response Team (RT-Z) in line with the existing zoonosis structure, in which Experts from human and veterinary health will conduct a risk assessment based on the new situation and share it online. 

Finally, the avian influenza situation in our country remains worrying. 

Unfortunately, outbreaks have occurred in recent weeks on both commercial poultry farms and hobby farms. 

Wild birds are also regularly found with avian influenza. 

The fact that a dairy cow has been infected with the avian influenza virus is therefore consistent with these times of high infection pressure. 

Nevertheless, this is a worrying development. I will therefore continue to closely monitor this situation and will conduct further research. I will inform you, together with the Minister of Health, Welfare and Sport, of relevant developments regarding avian influenza and this case. 

Sincerely, Femke Marije Wiersma, Minister of Agriculture, Fisheries, Food Security and Nature

Source: 

Links: Press Release, https://www.rijksoverheid.nl/onderwerpen/vogelgriep/nieuws/2026/01/23/antistoffen-vogelgriepvirus-gevonden-bij-melkkoe ; Parliamentary Document: https://www.rijksoverheid.nl/onderwerpen/vogelgriep/documenten/kamerstukken/2026/01/23/melkkoe-met-antistoffen-tegen-vogelgriep

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#Milk as a #Transmission Vehicle for Highly Pathogenic Avian #Influenza #H5N1

Abstract

Highly pathogenic avian influenza A (H5N1) (H5N1 hereafter) is an emerging pathogen in mammals. The recent recognition of H5N1 in dairy cattle increases opportunities for human exposure and infection and may accelerate a trajectory toward sustained human-to-human transmission. Furthermore, the presence of virus at high concentration in unpasteurized milk raises new risks for humans, especially infants and children. Milk has been identified as a vehicle for viral transmission in and between mammalian species, including humans. Sialic acids (SAs) found on cell surfaces are important mediators of species susceptibility to specific influenza strains and play an important role in viral tropism. New data demonstrate that SA receptors with α2,3 linkages capable of binding avian influenza strains are present in human mammary tissue. The presence of SA receptors that can bind avian influenza and a comparative analysis of viral transmission risk of raw and pasteurized milk in several mammalian species have implications for human milk feeding. During this period of sporadic human infections with H5N1, further research and collaboration is warranted to address the potential risk of human milk contamination. Infants and children are particularly vulnerable to emerging infections during pandemics and have unique needs that may be overlooked. Pandemic preparedness must address the needs of all populations at all life stages, including pregnancy and infancy, and must include support for the safety of human milk.

Source: 

Link: https://publications.aap.org/pediatrics/article-abstract/doi/10.1542/peds.2025-072525/206156/Milk-as-a-Transmission-Vehicle-for-Highly?redirectedFrom=fulltext

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#Infection and #transmission dynamics of #bovine and #human #influenza A #H5N1 viruses in mouse and hamster #models

 

Abstract

Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses: rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics, replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo. All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited significantly smaller plaques in bovine and human cells. In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared to the other strains. Similarly, as in the mouse experiments, in hamsters, all viruses induced body weight loss and oral shedding, with robust virus replication observed in tissues, but the rMichigan/90 virus presented reduced replication and shedding. Contact transmission studies in hamsters revealed limited transmissibility for these viruses, with only one out of four animals inoculated with the rMichigan/90 virus transmitting it to a naive contact. These findings indicate that both bovine- and human-derived H5N1 genotype B3.13 viruses present high pathogenicity in mammals, though the overall transmissibility remains low.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

College of Veterinary Medicine Research Office and the Office of the Vice Provost for Research, NIH/NIAID, 109022

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.17.700113v1

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Modeling of #H5N1 #influenza virus #kinetics during dairy #cattle #infection suggests the timing of infectiousness

 

Abstract

Since early-2024 unprecedented outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.4.4b have been ongoing in dairy cattle in the United States with significant consequences for the dairy industry and public health. Estimation of key epidemiological parameters is required to support outbreak response, including predicting the likely effectiveness of interventions and testing strategies. Here, we pool limited publicly available data from four studies of naturally and experimentally infected dairy cattle. We quantify Ct value trajectories of infected dairy cattle and the relationship between Ct value and the log-titer of infectious virus, a proxy for infectiousness. We estimate that following infection minimum Ct values are rapidly reached within 1–2 days with a population mean Ct value of 15.7 (12.9, 18.4). We identify a threshold Ct value of 21.8 (19.9, 24.6), with values of Ct value above this threshold representing little-to-no infectious viral load. Finally, assuming a direct relationship between Ct value and infectiousness, we estimate the distribution of the duration of infectiousness for dairy cattle (i.e., the duration their Ct value remains below the critical threshold) with a population median of 7.8 (4.1, 13.9) days. Our estimates will be critical inputs to the development of outbreak management guidelines and modeling analyses informing response strategies.

Source: 

Link: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003586

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#Polymerase #mutations underlie early #adaptation of #H5N1 #influenza virus to dairy #cattle and other #mammals

 

Abstract

In 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA resulting in spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells and tissues, as well as cells of other mammals including humans. We find evidence of several mammalian adaptations in cattle including PB2 M631L, which is found in all cattle sequences, and PA K497R, which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface, an essential host factor for viral genome replication. We show that this mutation adapts the polymerase to better interact with bovine ANP32 proteins, particularly ANP32A, and thereby enhances virus replication in bovine mammary systems and primary human airway cultures. We show that ongoing evolution in the PB2 gene, including E627K and a convergently arising D740N substitution, further increase polymerase activity and virus replication in a range of mammalian cells. Thus, circulation of H5N1 in dairy cattle allows virus adaption improving replicative ability in cattle and poses a continued risk of zoonotic spillover.

Source: 

Link: https://www.nature.com/articles/s41467-026-68306-6

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Natural #H5N1 #immunity in dairy #cows is durable and cross-protective but non-sterilizing

 

Abstract

Ongoing transmission of influenza A virus (H5N1) in U.S. dairy cattle threatens both animal and human health, underscoring the need to understand the durability of host immunity against reinfection with evolving genotypes. We challenged naive and convalescent cows, infected one year prior with H5N1 genotype B3.13, with either homologous B3.13 or heterologous D1.1 genotype virus. Homologous rechallenge resulted in complete clinical protection with no infectious viral shedding. Conversely, heterologous rechallenge led to transient clinical disease and limited infectious viral shedding. Convalescent cows experienced significantly milder disease than naive cows, which developed severe illness with high viral shedding and required early euthanasia, regardless of the strain. These findings indicate that naturally acquired immunity offers strong protection against severe illness but may allow silent transmission of divergent strains. Therefore, natural herd immunity alone is unlikely to eliminate the virus; controlling H5N1 in cattle will likely require vaccination strategies that address viral evolution.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Centers of Excellence for Influenza Research and Response (CEIRR), 75N93021C00016

National Institute of Allergy and Infectious Diseases, 75N93021C00016

National Institutes of Health, Department of Health and Human Services, 75N93021C00016

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.06.697911v1

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