Avian influenza publication – cattle


For studies of HPAI in birds, humans, mammals, please visit my main publications page

Examining the Survival of A(H5N1) Influenza Virus in Thermised Whole Cow Milk
https://www.biorxiv.org/content/10.1101/2025.03.05.641644v1
Multiple dairy products are made with unpasteurized but thermised milk  – does termisation work? 4 and 5 log10 reduction in infectivity at 60°C + 63°C, respectively. Viral infectivity was reduced to below the detection limit at 66°C. == effective.

Identification of Amino Acid Residues Responsible for Differential Replication and Pathogenicity of Avian Influenza Virus H5N1 Isolated from Human and Cattle in Texas, US
https://www.biorxiv.org/content/10.1101/2025.03.01.640810v1
Different outcomes b/w bovine H5N1, and human case of bovine H5N1. Human virus = enhanced polymerase activity vs bovine, in human cells. PB2 mutation E627K is major contributor. PB2 E362G, K627E affect morbidity, mortality, and viral replication.

Neutralizing Antibody Response to Influenza A(H5N1) Virus in Dairy Farm Workers, Michigan, USA
https://wwwnc.cdc.gov/eid/article/31/4/25-0007_article
MN and HI data from 2 human cases of HPAI = human HPAI virus infection, even in patients with clinically mild illness and localized infection, such as conjunctivitis, can induce neutralizing antibody responses

Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice
https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2475836
Comparison of 2344b from cows vs old clade 1 HPAI in mice: Cattle-H5N1 was highly lethal in mice (mLD50 =1.48PFU) with broad tissue tropism and produced higher titer in respiratory tissue and multiple extrapulmonary organs than VNM1194-H5N1. 

The impact of influenza A H5N1 virus infection in dairy cows
https://www.researchsquare.com/article/rs-6101018/v1
HPAI in cows. Clinical disease = 3 weeks, in ~20% of cattle. Seroprevalence = 89.4% in herd, with 76.1% of seropositive animals being subclinically infected. Milk losses of ~900 kg per cow. Economic loss = $737,500 for herd.

Timing and molecular characterisation of the transmission to cattle of H5N1 influenza A virus genotype D1.1, clade 2.3.4.4b
https://virological.org/t/timing-and-molecular-characterisation-of-the-transmission-to-cattle-of-h5n1-influenza-a-virus-genotype-d1-1-clade-2-3-4-4b/991
Analysis suggests H5N1 D1.1 genotype may have jumped to Nevada cows weeks before detection
https://www.cidrap.umn.edu/avian-influenza-bird-flu/analysis-suggests-h5n1-d11-genotype-may-have-jumped-nevada-cows-weeks

Pasteurisation temperatures effectively inactivate influenza A viruses in milk
https://link.springer.com/article/10.1038/s41467-025-56406-8
Already reviewed as a preprint.
Pasteurisation effective for inactivation of human + avian influenza, influenza D, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins. infectivity rapidly lost + undetectable before recommended pasteurisation time.

A mathematical model of H5N1 influenza transmission in US dairy cattle
https://www.medrxiv.org/content/10.1101/2025.01.28.25321250v1
Modelling to elucidate outbreak on cattle. Dynamics in states are dependent on composition of the dairy sector. Model calculates outbreak beyond just reporting, and identifies key data required to model the outbreak.

Intraductal infection with H5N1 clade 2.3.4.4b influenza virus
https://journals.asm.org/doi/10.1128/jvi.01927-24?s=03
# reviewed as a preprint. Intraductal (ie, via udder) inoculation of H5N1 but not H1N1 influenza virus results in infection in mice

In laboratory inactivation of H5N1 in raw whole milk through milk acidification: results from a pilot study
https://www.sciencedirect.com/science/article/pii/S0022030225000517
Beyond pasteurisation, milk acidification (pH 4.1-4.2) = inactivation of LPAI H6N2 + HPAI H5N1 virus in milk after 6h. Lactoperoxidase system (LPS) was not effective.

Raw milk, bird flu, and the politicisation of public health
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00024-6/fulltext
News article on investigation into AIV in raw milk products in the US & associated regulatory/political conflicts.

Testing of Retail Cheese, Butter, Ice Cream, and Other Dairy Products for Highly Pathogenic Avian Influenza in the US
https://www.sciencedirect.com/science/article/pii/S0362028X24002151
Reviewed as a preprint. HPAI prolific in dairy products in the USA – 17.4% (29/167) had detectable viral RNA but no live virus. Results support pasteurization effectively inactivating HPAI in dairy products.

No Evidence of Anti-influenza Nucleoprotein Antibodies in Retail Milk from Across Canada (April – July 2024)
https://www.medrxiv.org/content/10.1101/2025.01.31.25321461v1
Updated preprint outlining testing from the Canadians. Still no evidence for HPAI in cattle there via national milk testing.  

Viral kinetics of H5N1 infections in dairy cattle
https://www.biorxiv.org/content/10.1101/2025.02.01.636082v1
Modelling of data from publicly available data from 3 studies of naturally + experimentally infected cattle, with a focus on Ct value trajectories. Peak Ct at 1-2dpi, and infectious load threshold at Ct as low as 21 which is suspicious. Authors are modellers, and not involved in cattle outbreaks. Based on 3 studied. 

Influenza A(H5N1) Viruses Isolated From Dairy Cattle Demonstrate High Virulence in Laboratory Models, but Retain Avian Virus-like Properties
https://www.researchsquare.com/article/rs-5806806/v1
Cow HPAI: lethal in mice + ferrets, transmitted by direct but not airborne contact ferrets. All replicated in human bronchial epithelial cells, despite avian receptor pref. risk of cattle viruses to humans not in contact with affected animals is low.

Evaluation of humoral immune response and milk antibody transfer in calves and lactating cows vaccinated with inactivated H5 avian influenza vaccine
https://www.nature.com/articles/s41598-025-87831-w
Lactating cattle and calves vaccinated using oil adjuvant inactivated. dose-dependent immune response: ???? doses = stronger + more sustained antibody levels. Milk antibody transfer detected, strongest at 2 weeks pv.
Despite being an cow experiment, its published in Sci Reports, and the data analysis isnt detailed… 

mGem: Transmission and exposure risks of dairy cow H5N1 influenza virus
https://journals.asm.org/doi/10.1128/mbio.02944-24
Really nice overview of the HPAI situation in US dairy cattle, with a focus on transmission modalities between cows within herds, the spread of the virus between dairy farms, and exposure risks for humans. Highlights key gaps.

Risk Assessment of Spread of the Influenza A Virus in Cows in South Bulgaria
https://www.mdpi.com/1999-4915/17/2/246
559,544 cattle are bred in Bulgaria, with 12,439 dairy farms producing 748,278 thousand liters. Here a risk assessment of virus spillover and consequences for the Bulgarian dairy industry.

Transmission of highly pathogenic avian influenza H5N1 to calves fed unpasteurized milk from experimentally infected cows
https://www.cabidigitallibrary.org/doi/10.31220/agriRxiv.2025.00303
Viruses from infected dairy cattle can be passed to calves via milk. Calves fed infected milk = nasal discharge, mild fever, mild lethargy, loose stool, slightly increased respiratory effort for 5-6 days. Difficult to diagnose. Positive nasal swabs.

Receptor binding, structure, and tissue tropism of cattle-infecting H5N1 avian influenza virus hemagglutinin
https://www.cell.com/cell/abstract/S0092-8674(25)00048-0?rss=yes&utm_medium=twitter&utm_source=dlvr.it
Bovine HPAI still favors avian receptors, but slight human receptor affinity, strongly bind to both bovine + human conjunctival, tracheal, mammary tissues = indicating a risk for human transmission

The Haemagglutinin Gene of Bovine-Origin H5N1 Influenza Viruses Currently Retains Receptor-binding and pH-fusion Characteristics of Avian Host Phenotype
https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2451052
HA genes from the bovine HPAI do not pose enhanced threat compared to avian HPAI = all tested viruses and mutations binding to to avian receptors, pH fusion of 5.9 = outside pH range for efficient human airborne transmission.
Popular Science: https://www.pirbright.ac.uk/news/bird-flu-cattle-not-increased-threat-humans

Susceptibility of bovine respiratory and mammary epithelial cells to avian and mammalian derived clade 2.3.4.4b H5N1 highly pathogenic avian influenza viruses
https://www.biorxiv.org/content/10.1101/2025.01.09.632235v1.abstract
Bovine mammary epithelial cells and swine respiratory epithelial cells permissive to both avian and mammalian HPAI strains. Sialic acid expression a factor in cell type, with increased sialic acid expression in tissues with more virus binding. Also differences in sialic acid expression bw dairy + beef cattle respiratory tissues.

A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth
https://www.nature.com/articles/s41467-024-54934-3
A/Texas/37/2024, human virus from bovine outbreak: ???? binding breadth to core glycans w α2,3 (avian) sialic acids, none to α2,6 (mammal). Also more flexible in RBD, and T199I, is responsible for increased binding breadth

Polymerase mutations underlie adaptation of H5N1 influenza virus to dairy cattle and other mammals.
https://www.biorxiv.org/content/10.1101/2025.01.06.631435v1
cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes = better replication in bovine cells, + other mammalian species including humans and pigs: PB2 M631L, PA K497R and PB2 D740N

Highly pathogenic avian H5N1 influenza A virus replication in ex vivo cultures of bovine mammary gland and teat tissues
https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2450029#d1e346
Cow H5N1, chicken H5N1, H1N1 2009 in mammary gland/teat cells: viruses use 2/3 avail lectins, cow H5N1 had much higher titres, replicated in alveoli, gland, and teat cisterns

The Uncleaved Viral Hemagglutinin HA0 Increases Influenza A Virus Resistance to Thermal Pasteurization 
https://www.sciencedirect.com/science/article/abs/pii/S0042682225000017
Avian and human influenzas heat treated: avian viruses  more stable at 75°C than human viruses, inactive virus preparations w HA0 protein retained infectious long during heat treatment +regained infectivity after heat inactivation by adding trypsin

Pasteurized retail dairy enables genomic surveillance of H5N1 avian influenza virus in United States cattle
https://www.medrxiv.org/content/10.1101/2024.12.12.24318872v1
With limited testing of dairy herds, there is an unmet need for genomic surveillance. Here, tiled-amplicon approach = 90% genome coverage < 20x depth from 5/13 positive dairy products. Useful to sequence if you cant reach the cows…. But better if you could test the cows!

Longitudinal screening of retail milk from Canadian provinces reveals no detections of influenza A virus RNA (April–July 2024): leveraging a newly established pan-Canadian network for responding to emerging viruses
https://cdnsciencepub.com/doi/10.1139/cjm-2024-0120
No evidence for HPAI in Canadian cattle from testing of retail milk across the provinces (April – July 2024). 

Highly pathogenic avian influenza virus H5N1 infection in dairy cows confers protective immunity against reinfection
https://www.researchsquare.com/article/rs-5613077/v1
Cattle inoculated with HPAI in hindquarter of udders. 31 days laters, inoculated in front quarter of udders. Prior infection = complete protection from both mastitis and virus replication and shedding in the forequarters of the udder. 

Replication Kinetics, Pathogenicity and Virus-induced Cellular Responses of Cattle-origin Influenza A(H5N1) isolates from Texas, United States
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2447614
Previously reviewed as preprint. 
A/Texas/37/2024 replicated more efficiently than A/bovine/Texas/24-029328-02/2024 in mammalian and avian cells. The high path, (and modfieid low path) human virus exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice compared to the bovine strain

Detection and Phylogenetic Characterization of Influenza D in Swedish Cattle
https://www.mdpi.com/1999-4915/17/1/17
1763 samples from 2021-2024 in Sweden: 51 Influenza D virus positives in cows with resp signs. Two different clades, including reassortants. First detections for Sweden. Influenza D probably widespread, and very much understudied.

Modeling the Transmission Dynamics of Avian Influenza in Cattle
https://www.sabapub.com/index.php/jmam/article/view/1214
Paper describing a mathematical model. Unclear what the input data was, or if its just a conceptual model. Perhaps interesting to modellers, too maths for me.

Establishing methods to monitor H5N1 influenza virus in dairy cattle milk
https://www.medrxiv.org/content/10.1101/2024.12.04.24318491v1?ct=
Optimized detection+ sequencing for H5N1 surveillance in milk. Digital PCR strongly correlated with qPCR Cts, wdPCR exhibiting greater sensitivity. metagenomic sequencing after hybrid selection for higher conc vs amplicon sequencing for low conc

A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciae576/7920653
In Texas dairy farm: 64% (9/14) of milk, 2.6% (1/39) of cattle nasal swabs, 0/17 cattle worker nasopharyngeal swab specimens pos for HPAI. 14% of sera from workers antibody positive. Detected SARS-CoV-2 in a nasal swab from a sick cow

Testing of retail cheese, butter, ice cream and other dairy products for highly pathogenic avian influenza in the US
https://www.sciencedirect.com/science/article/pii/S0362028X24002151
HPAI in milk, cheese, butter, and ice cream, but confirmatory testing found no live virus in any sample (=pasteurization effective). Sequenced virus == bovine outbreak.

Rapid and Safe Neutralization Assay for Circulating H5N1 Influenza Virus in Dairy Cows
https://onlinelibrary.wiley.com/doi/10.1111/irv.70048
Neutralization assay using luminescent virus-like particles. Detection of neutralizing antibodies induced by clade 2.3.4.4b candidate vaccine viruses with the cow-derived H5N1 virus = potential efficacy of vaccines using current CVVs

Susceptibility of calf lung slice cultures to H5N1 influenza virus
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2432368
ex vivo lung slice cultures from calves provide a useful method to rapidly screen host susceptibility to a range of influenza A viruses

A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors
https://www.science.org/doi/10.1126/science.adt0180
HPAI in cattle still preferentially binds to avian (vs mammalian) receptors. The switch to mammalian receptors can occur in 1 mutation: Gln226Leu. 

POLYGENIC DETERMINANTS OF H5N1 ADAPTATION TO BOVINE CELLS
https://www.biorxiv.org/content/10.1101/2024.11.29.626120v1
Contribution of viral “internal” genomic segments of H5N1 B3.13 to bovine cells adaptation. Generated recombinants with dif genotypes: recombinant B3.13 viruses displayed faster replication kinetics in bovine cells compared to other IAV

The Thermal Stability of Influenza Viruses in Milk
https://www.mdpi.com/1999-4915/16/11/1766
Pasteurisation inactivates HPAI in milk. Also works for influenza D viruses. 

Intramammary infection of bovine H5N1 influenza virus in ferrets leads to transmission and mortality in suckling neonates
https://www.biorxiv.org/content/10.1101/2024.11.15.623885v2
Its not just cows – lactating ferrets transmit HPAI H5N1 to suckling kits. Viral RNA titers high in milk over time and remained high in mammary gland tissue. Viral titres in dam nasal swabs delayed, and minimally present in oral swabs.

Enhanced encephalitic tropism of bovine H5N1 compared to the Vietnam H5N1 isolate in mice
https://www.biorxiv.org/content/10.1101/2024.11.19.624162v2
Comparing human case H5N1 from cows and from birds (Vietnam/2004) uniformly lethal in mice. Cow: resp tract + brain, CNS infection, Bird: only resp tract >> diff tissue tropism.

Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission
https://journals.asm.org/doi/10.1128/mbio.02542-24
Review of origin, evolution and cross species transmission of HPAI H5N1 in dairy cattle.

Environmental stability of HPAIV H5N1 in raw milk, wastewater and on surfaces
https://www.biorxiv.org/content/10.1101/2024.10.22.619662v1.abstract
Half-life of H5N1 in raw milk (2.1 days), on polypropylene (1.4 days) and stainless-steel surfaces (1.2 days), wastewater (0.48 days).  Detectable quantities of infectious virus could theoretically persist in refrigerated raw milk for 45 days.

Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets
https://www.nature.com/articles/s41586-024-08246-7
A/Texas/37/2024 (TX/37) A(H5N1) virus isolated from dairy farm worker in Texas

  • maintaining an avian-like receptor binding specificity
  • robust systemic infection in ferrets, w high levels of virus shedding
  • severe and fatal infection, characterised by viremia and extrapulmonary spread
  • efficient transmission in a direct contact setting
  • capable of indirect transmission via fomites

A human isolate of bovine H5N1 is transmissible and lethal in animal models
https://www.nature.com/articles/s41586-024-08254-7
A/Texas/37/2024 (TX/37) A(H5N1) virus isolated from dairy farm worker in Texas

  • Effective replication in primary human alveolar epithelial cells, less efficiently in corneal epithelial cells. 
  • Lethal in mice & ferrets, spread systemically with high titres in respiratory & non-respiratory organs. 
  • Effectively transmitted in ferrets via respiratory droplets in 17%–33% of transmission pairs. 5/6 infected ferrets died. 
  • PB2-631L (encoded by bovine isolates), promoted influenza polymerase activity in human cells, suggesting a role in mammalian adaptation like PB2-627K (encoded by huTX37-H5N1). 
  • Bovine HPAI H5N1 viruses susceptible to polymerase inhibitors both in vitro & in mice. 

Replication Kinetics, Pathogenicity and Virus-induced Cellular Responses of Cattle-origin Influenza A(H5N1) Isolates from Texas, United States
https://www.biorxiv.org/content/10.1101/2024.10.29.620905v1?ct=
A/Texas/37/2024 replicated more efficiently than A/bovine/Texas/24-029328-02/2024 in mammalian and avian cells. The high path, (and modfieid low path) human virus exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice compared to the bovine strain.

Orogastric Exposure of Cynomolgus Macaques to Bovine HPAI H5N1 Virus Results in Subclinical Infection
https://www.researchsquare.com/article/rs-5182487/v1
Intranasal/intratracheal inoculation of H5N1 in macaques = systemic infection w mild and severe respiratory disease. Infection via orogastric route = subclinical, limited infection and seroconversion

Survivability of H5N1 Avian Influenza Virus in Homemade Yogurt, Cheese and Whey
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2420731
Preprint now available in press.. No viable H5N1 in spiked dairy used to make whey, cheese & yoghurt 

Efficacy of oseltamivir and baloxavir against A(H5N1)-contaminated bovine milk in mice
https://www.researchsquare.com/article/rs-5119512/v1
Baloxavir treatment in mice has better disease outcomes compared to oseltamivir after being infected with milk containing H5N1. Better mouse survival, lower organ titres.

Dairy cows inoculated with highly pathogenic avian influenza virus H5N1
https://www.nature.com/articles/s41586-024-08166-6
Experimental infection of cattle with HPAI by the American team:
– Heifers inocculated by aerosol respiraotry route, mild clinical disease, but lesions+seroconvertion
– Cattle innoculated via intramammary route. Clinical disease, decreased rumen motility, changes to milk appearance, production losses, high levels of viral RNA detected in milk, virus isolation, lesions in mammary tissue, and seroconversion

Infectivity and persistence of influenza viruses in raw milk
https://www.medrxiv.org/content/10.1101/2024.10.10.24315269v1
An interesting take – they tested PR8 (lab strain of human influenza) in milk. infectious in raw milk for up to 5 days, viral RNA remained detectable and stable for at least 57 days, with no significant degradation. Pasteurization significantly reduced detectable viral RNA 

Influenza A(H5N1) Virus Resilience in Milk after Thermal Inactivation
https://wwwnc.cdc.gov/eid/article/30/11/24-0772_article
PR8 and a diversity of H5N1 viruses spiked into in retail and unpasteurized milk revealed virus resilience under certain conditions, but are inactivated under pasteurisation conditions.

The mammary glands of cows abundantly display receptors for circulating avian H5 viruses
https://journals.asm.org/doi/10.1128/jvi.01052-24
Mammary glands of cows display receptors for 2.3.4.4b H5 viruses, but respiratory tract does not = may explain tropism for mammary glands

Hot topic: Epidemiological and clinical aspects of highly pathogenic avian influenza H5N1 in dairy cattle
https://www.sciencedirect.com/science/article/pii/S2666910224001534 
Review of epidemiological & clinical aspects of HPAI H5N1 in cattle. Includes discussion on surveillance & control measures to implement within herds. Identifies areas where further research is needed.

Hot topic: Influenza A H5N1 virus exhibits a broad host range, including dairy cows
https://www.sciencedirect.com/science/article/pii/S2666910224001546
Review of host range of avian influenza, and infection dynamics in cattle.

Hot topic: Avian influenza subtype H5N1 in US dairy—A preliminary dairy foods perspective
https://www.sciencedirect.com/science/article/pii/S2666910224001522
Review of HPAI in milk and dairy, and impact of pasteurisation.

Rapid evolution leads to extensive genetic diversification of cattle flu Influenza D virus
https://www.nature.com/articles/s42003-024-06954-4
Up to 80% cattle seropositive for influenza D virus. Five genetic lineages. Reassortment of IDV in US,  transboundary circulation in Europe. Higher rate of evolution and uncontrolled circulation, could facilitate its adaptation to humans.

H5N1 clade 2.3.4.4b dynamics in experimentally infected calves and cows
https://www.nature.com/articles/s41586-024-08063-y
Results from the FLI cow experimental infections and it is a tour-de-force. 

  •  Calves: moderate nasal replication + shedding with no severe clinical signs. No transmission to sentinel calves
  • Dairy cows: no nasal shedding, high fever, severe acute mammary gland infection with necrotizing mastitis. No systematic infection
  • Milk production was rapidly and drastically reduced and the physical condition of the cows was severely compromised. Virus titers in milk rapidly peaked at 108 TCID50/mL
  • both H5N1 euDG + B3.13 successfully replicated in cattle udders without respiratory spread

Thermal inactivation spectrum of influenza A H5N1 virus in raw milk
https://www.biorxiv.org/content/10.1101/2024.09.21.614205v1.abstract
Decay and thermal stability spectrum of HPAI H5N1 virus in raw milk:  long term stability in raw 91 milk at 4oC but is rapidly inactivated by pasteurization

Wastewater Surveillance for Influenza A Virus and H5 Subtype Concurrent with the Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in Cattle and Poultry and Associated Human Cases — United States, 
https://www.cdc.gov/mmwr/volumes/73/wr/mm7337a1.htm

Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Viruses in U.S. Dairy Cattle and Detection of Two Human Cases — United States, 2024
https://www.annemergmed.com/article/S0196-0644(24)00437-2/abstract
Abridged version of an MMWR Morb Mortal Wkly Rep shared earlier.

Bovine Highly Pathogenic Avian Influenza Virus Stability and Inactivation in the Milk Byproduct Lactose
https://www.mdpi.com/1999-4915/16/9/1451
H5N1 virus stable for 14 days in a concentrated lactose solution under refrigerated conditions. Heat or citric acid treatments successfully inactivated the virus in lactose.

Personal Protective Equipment Guidance for Highly Pathogenic Avian Influenza H5N1 Should Be Adapted to Meet the Needs of Dairy Farm Workers
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae380/7758743?login=true
Michigan targeting dairy workers with simplified PPE guidance for improved likelihood of adherence. Recommend specifically addressing high-risk practices observed on dairy farms.

Detection and Monitoring of Highly Pathogenic Influenza A Virus 2.3.4.4b Outbreak in Dairy Cattle in the United States
https://www.mdpi.com/1999-4915/16/9/1376
Evaluation of HPAI antibodies in serum and milk and viral RNA in milk on dairy farms in Texas, Kansas, and Michigan. Positive correlation between paired serum and milk sample results. high diagnostic performance during the convalescent phase.

Avian and Human Influenza A Virus Receptors in Bovine Mammary Gland
https://wwwnc.cdc.gov/eid/article/30/9/24-0696_article
Publication of a preprint previously included. Detected IAV sialic acid -α2,3/α2,6-galactose host receptors in bovine mammary glands by lectin histochemistry. Results provide a rationale for high levels of H5N1 virus in milk from infected cows.

The highly pathogenic H5N1 virus found in U.S. dairy cattle has some characteristics that could enhance infection and transmission among mammals
https://www.nature.com/articles/s41684-024-01425-z
News and Views paper about the Ensfield nature paper. 

Recent Bovine HPAI H5N1 Isolate is Highly Virulent for Mice, Rapidly Causing Acute Pulmonary and Neurologic Disease
https://www.biorxiv.org/content/10.1101/2024.08.19.608652v1
Inoculation of C57BL/6J and BALB/c mice with HPAI resulted in virus replication in the lung inducing severe respiratory disease, C57BL/6J mice infected with the bovine isolate also developed high virus titers in the brain. Bovine isolate possesses enhanced respiratory and neuroinvasive/neurovirulent properties

Inactivation of highly pathogenic avian influenza virus with high temperature short time continuous flow pasteurization and virus detection in bulk milk tanks
https://www.sciencedirect.com/science/article/pii/S0362028X24001339?via%3Dihub 
Publication of a report previously included.
Very high virus titre in bulk tank milk from affected regions. Heating from 40°C to 72.5°C in 9.9 seconds reduced virus to undetectable levels. = Pasteurisation effective..

Notes from the Field: Health Monitoring, Testing, and Case Identification Among Persons Exposed to Influenza A(H5N1) — Michigan, 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7329a4.htm?s_cid=mm7329a4_w
As of May 23, 2024, Michigan had largest number of affected dairy & poultry facilities linked to HPAI A(H5N1) outbreak. Active symptom monitoring and testing of exposed workers led to detection of 2nd and 3rd known dairy-associated HPAI A(H5N1) cases in 2024.

Enhanced replication of contemporary human highly pathogenic avian influenza H5N1 virus isolate in human lung organoids compared to bovine isolate
https://www.biorxiv.org/content/10.1101/2024.08.02.606417v1
Compared virus replication & host responses in human alveolar epithelium infected with HPAI H5N1 viruses. A/Vietnam/1203/2004 replicated most efficiently, followed by A/Texas/37/2024, then A/bovine/Ohio/B24OSU-342/2024 → cattle viruses just not that efficient at infecting humans compared to human viruses. 

Bovine H5N1 influenza virus binds poorly to human-type sialic acid receptors
https://www.biorxiv.org/content/10.1101/2024.08.01.606177v1
Despite large number of birds and cattle affected, few human cases of 2344b. Here, evidence that avian and bovine H5N1 influenza virus binds poorly to human-type sialic acid receptors.

Influenza A(H5N1) Virus Infection in Two Dairy Farm Workers in Michigan
https://www.nejm.org/doi/full/10.1056/NEJMc2407264
“Case report on the human infections. 

Highly pathogenic H5N1 avian influenza virus outbreak in cattle: the knowns and unknowns
https://www.nature.com/articles/s41579-024-01087-1
By Neumann and Kawaoka, so definitely the paper to read. Short and to the point summary of the current situation.

Strain-dependent variations in replication of European clade 2.3.4.4b influenza A(H5N1) viruses in bovine cells and thermal inactivation in semi-skimmed or whole milk
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2024.29.30.2400436
Strain-dependent differences of H5N1 in thermal inactivation, particularly in whole milk. All H5N1 viruses and H10 (with trypsin) replicated efficiently in bovine cells, but pigeon and red knot viruses exhibited lower titres,.

Fucosylated and non-fucosylated alpha2,3 sialosides were detected on the bovine mammary gland tissues
https://www.biorxiv.org/content/10.1101/2024.07.29.605565v1
Analyzed of the detailed receptor distributions of bovine mammary gland using recombinant HA’s rather than plant-derived lectins which have been used in other studies and may not be that appropriate.. Detection of fucosylated and nonfucosylated α 2,3 sialosides.

A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms
https://www.medrxiv.org/content/10.1101/2024.07.27.24310982v1
Sampled cattle, milk and workers. Found HPAI in cattle swabs, milk, but none in workers. Found antibodies against HPAI in some workers (small sample size). But.. they found SARS-CoV-2 in a nasal swab of a cow. What a mess. 
Pop Sci: https://www.npr.org/sections/shots-health-news/2024/07/31/nx-s1-5059071/bird-flu-human-cases-farm-workers-testing 
>>> ~15% farm workers tested (n=14) seropositive for HPAI in Texas. None in Michagan. 
Repsonse from Florian Krammer: “This was measured by MN assay, not HAI. Titers of positives were low. Could as well be crossreactive anti-stalk or anti-N1 antibodies from seasonal H1N1 infections.: https://x.com/florian_krammer/status/1818732155733692690 

Colorado orders weekly bulk tank avian flu testing for dairy farms
The state has now reported 49 outbreaks in dairy cows, nearly half of its licensed dairy farms
https://www.cidrap.umn.edu/avian-influenza-bird-flu/colorado-orders-weekly-bulk-tank-avian-flu-testing-dairy-farms

Notes from the Field: Health Monitoring, Testing, and Case Identification Among Persons Exposed to Influenza A(H5N1) — Michigan, 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7329a4.htm

Evaluation of the Humoral Immune Response and Milk Antibody Transfer in Cattle vaccinated with inactivated H5 Avian Influenza vaccine
https://www.researchsquare.com/article/rs-4627508/v1
Calves inoculated with different vaccine doses, while lactating cows received the vaccine four weeks later. Dose-dependent immune response. Higher doses = stronger & more sustained antibody levels against HPAI 2.3.4.4b. Milk antibody transfer observed. Strong positive responses in milk samples by second week post-vaccination.

Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle
https://www.nature.com/articles/s41586-024-07849-4
Press release: https://www.eurekalert.org/news-releases/1052083 
Paper includes a few preprints into 1 now and is probably the one to cite moving forward. Includes spillover, clincial signs, milk detection, tropism of mammary glands, multidirectional interspecies transmissions.  This paper has gotten loads of media coverage, with “mammal-to-mammal transmission” in the title of almost every story.

Effectiveness of Pasteurization for the Inactivation of H5N1 Influenza Virus in Raw Whole Milk
https://www.medrxiv.org/content/10.1101/2024.07.23.24310825v1
By the Canaadian team – similar to other studies: complete inactivation of H5N1 spiked raw milk at 63C for 30 minutes. Complete viral inactivation observed in 7/8 replicates of raw milk samples treated at 72C for 15 seconds. Pasteurization effective.

CDC Birdflu Response 
https://www.cdc.gov/bird-flu/spotlights/h5n1-response-07192024.html
>> Total of 10 human cases of 2.3.4.4b in USA – some from dairy cows, some from poultry

Experimental reproduction of viral replication and disease in dairy calves and lactating cows inoculated with highly pathogenic avian influenza H5N1 clade 2.3.4.4b
https://www.biorxiv.org/content/10.1101/2024.07.12.603337v1
Experimentally Holstein yearling heifers & lactating cows with cow HPAI. Heifers via aerosol respiratory route & cows by intramammary route. Mild clinical disease in heifers. Clinical disease in lactating cows = decreased rumen motility, changes to milk appearance, production losses consistent with field reports of viral mastitis. 

Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm
https://link.springer.com/article/10.1007/s11262-024-02085-4
HPAIV H5N1 from environmental swab samples collected from a dairy farm in the state of Kansas, USA. PB2 E249G, NS1 R21Q pres, 1.7%  reads w PB2 (E627K).

Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2380421
HPAI viruses from dairy cattle w abrupt milk drop, two cats, six wild birds, and one skunk = early identical genome sequences B3.13.

CDC A(H5N1) Bird Flu Response Update, July 5, 2024
https://www.cdc.gov/bird-flu/spotlights/h5n1-response-07052024.html

Stop H5N1 influenza in US cattle now
https://www.science.org/doi/10.1126/science.adr5866
Great piece by Nicola Lewis & Martin Beer: “Even difficult viral adaptations can occur if there are enough opportunities for contact and replication in new host species. Adaptation of the virus to cattle must be prevented.”

Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Viruses in U.S. Dairy Cattle and Detection of Two Human Cases — United States, 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7321e1.htm?ACSTrackingID=USCDC_921-DM129096&ACSTrackingLabel=Early%20Release%20%E2%80%93%20Vol.%2073%2C%20May%2024%2C%202024&deliveryName=USCDC_921-DM129096
350 exposed farm workers being monitored; one of the two cases was identified via daily, active monitoring. Surveillance identified no unusual IAV activity trends in U.S.. A(H5) candidate vaccine viruses available. Lab analyses indicate A(H5N1) viruses circulating in cows & other animals susceptible to FDA-approved antivirals.

Surveillance of H5 HPAI in Michigan using retail milk
https://www.biorxiv.org/content/10.1101/2024.07.04.602115v2
qPCR detection of IAV in milk from local markets across Michigan. 2/13 samples +ve for IAV nucleic acid. Milk-based surveillance potentially useful if applied systematically at dairy processors or point of sale.

Inactivation of Avian Influenza Virus Inoculated into Ground Beef Patties Cooked on a Commercial Open-Flame Gas Grill
https://www.sciencedirect.com/science/article/pii/S0362028X24001091?via%3Dihub
USDA FSIS recommended minimum internal temperature of 71.1°C for ground beef reduced AIV levels to below detection.

Pathogenicity and transmissibility of bovine H5N1 influenza virus
https://www.nature.com/articles/s41586-024-07766-6
This article has garnered lots of attention – the results of mice and ferret experiments of H5N1. Viruses found in mammary glands of both mice and ferrets + resp tract of ferrets. Inefficient transmission in ferrets
Sci comm: Animal experiments shed more light on behaviour of H5N1 from dairy cows
https://www.cidrap.umn.edu/avian-influenza-bird-flu/animal-experiments-shed-more-light-behavior-h5n1-dairy-cows
Sci comm: https://www.nih.gov/news-events/news-releases/features-h5n1-influenza-viruses-dairy-cows-may-facilitate-infection-transmission-mammals 

Health officials pitch anonymous bird flu testing
https://www.axios.com/2024/07/10/bird-flu-virus-cows-anonymous-testing
Farmers refusing to test herds fearing economic consequences. Anonymous testing could mean results from individual farms anonymized & sent to U.S. Department of Agriculture. Challenge of zeroing in & addressing transmission at source would still remain.

H5N1 avian influenza in USA: A call for vigilance in one health surveillance
https://www.sciencedirect.com/science/article/pii/S2590170224000293
Although immediate public health risk posed by H5N1 currently low, human infection in Texas reinforces importance of One Health approach.

Pasteurization Inactivates Highly Infectious Avian Flu in Milk
https://asm.org/Press-Releases/2024/July/Pasteurization-Inactivates-Highly-Infectious-Avian

Characterization of highly pathogenic avian influenza virus in retail dairy products in the US
https://journals.asm.org/doi/10.1128/jvi.00881-24
Publication of pre-print already reviewed

Inactivation of highly pathogenic avian influenza virus with high temperature short time 1 continuous flow pasteurization and virus detection in bulk milk tanks 
https://www.fda.gov/media/179708/download?attachment
Evaluated HPAIV inactivation in artificially contaminated raw milk using most common legal conditions in US: 72°C for 15s. No viable virus detected. 

Bird flu in wastewater
https://www.nature.com/articles/s41587-024-02297-x
Data from May 5–18 from 281 sampling locations show ^ levels of IAV virus at 3 sites in 2 states, & further 2 states where levels were ^ average compared with historic baseline samples.

H5N1 clade 2.3.4.4b avian influenza viruses replicate in differentiated bovine airway epithelial cells cultured at air-liquid interface
https://doi.org/10.1099/jgv.0.002007
Bovine cells + European HPAI H5N1: ????viral genome loads + infectious virus in 1st 24 h post-inoculation w/out cytopathogenic effects. infected cells still detectable by immunofluorescent staining @ 3dpi. =multiple lineages can infect resp tract of cattle

A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth
https://www.biorxiv.org/content/10.1101/2024.06.22.600211v1
HPAI human case ^ binding to α2,3 sialic acids (avian receptor) compared to historical & recent 2.3.4.4b H5N1 viruses. No binding to α2,6 sialic acids yet (mammalian recept). Single mutation outside receptor binding site T199I responsible for increased binding breadth

CDC: H5N1 Bird Flu Confirmed in Person Exposed to Cattle
https://jamanetwork.com/journals/jama/article-abstract/2818256

Detection of A(H5N1) influenza virus nucleic acid in retail pasteurized milk
https://www.researchsquare.com/article/rs-4572362/v1
Testing of pasteurized milk from retail in USA: HPAI in 36.3%. No evidence of viable virus was found following inoculation of MDCK cells, embryonated chicken eggs, or mice.

H5N1 clade 2.3.4.4b avian influenza viruses replicate in differentiated bovine airway epithelial cells cultured at air-liquid interface
https://doi.org/10.1099/jgv.0.002007
Experimental infection of cow epithelial cells. 1st 24 hrs: ???? viral genome loads + infectious virus + no cytopathogenic effects. 3dpi: infected cells by immunoflourescnece. == can infect cattle resp tract.

Technical Report: June 2024 Highly Pathogenic Avian Influenza A(H5N1) Viruses
https://www.cdc.gov/bird-flu/php/technical-report/h5n1-06052024.html?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/spotlights/2023-2024/h5n1-technical-report-06052024.htm
> Summary by Flu Trackers: https://flutrackers.com/forum/forum/national-international-government-ngo-preparation-response/cdc/h5n1-information/992090-cdc-a-h5n1-bird-flu-response-update-june-14-2024 
> CDC analysed sera (blood) collected from people of all ages in all 10 HHS regions. Blood samples were collected during the 2022-2023 and 2021-2022 flu seasons. These samples were challenged with H5N1 virus to see whether there was an antibody reaction. Data from this study suggest that there is extremely low to no population immunity to clade 2.3.4.4b A(H5N1) viruses in the United States. Antibody levels remained low regardless of whether or not the participants had gotten a seasonal flu vaccination, meaning that seasonal flu vaccination did not produce antibodies to A(H5N1) viruses. This means that there is little to no pre-existing immunity to this virus and most of the population would be susceptible to infection from this virus if it were to start infecting people easily and spreading from person-to-person. This finding is not unexpected because A(H5N1) viruses have not spread widely in people and are very different from current and recently circulating human seasonal influenza A viruses.

Inactivation rate of highly pathogenic avian influenza H5N1 virus (clade 2.3.4.4b) in raw milk at 63 and 72 degrees Celsius
https://www.nejm.org/doi/full/10.1056/NEJMc2405488#
Press release summary: https://www.nih.gov/news-events/news-releases/infectious-h5n1-influenza-virus-raw-milk-rapidly-declines-heat-treatment 
>heat treatment at 63°C would yield a decrease in infectious viral titer by a factor of 10^10 within 2.5 minutes = standard bulk pasteurization of 30 minutes at 63°C has a large safety buffer
> small but detectable quantity of HPAI A(H5N1) virus to remain infectious in milk after 15 seconds at 72°C if the initial titer is sufficiently high

Sialic Acid Receptor Specificity in Mammary Gland of Dairy Cattle Infected with Highly Pathogenic Avian Influenza A(H5N1) Virus
https://wwwnc.cdc.gov/eid/article/30/7/24-0689_article
The respiratory and mammary glands ofdairy cattle are rich in sialic acids, particularly avian α2,3-gal. Mammary gland tissues co-stained with sialic acids and influenza A virus nucleoprotein showed predominant co-localization with the virus and SA α2,3-gal.

Bird Flu Outbreak in Dairy Cows Is Widespread, Raising Public Health Concerns
https://jamanetwork.com/journals/jama/article-abstract/2818724
Summary of events in cattle, touching on all the key points. 

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155697/
Summary of epidemiology, transmission, and surveillance of HPAI H5N1 subtype in birds, mammals, and dairy cows, and why there are concerns regarding transmission to humans.

Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA
https://wwwnc.cdc.gov/eid/article/30/7/24-0717_article
Case report of early outbreak in cattle. Lots of interesting insights into how they worked it all out.

CDC Reports A(H5N1) Ferret Study Results
https://www.cdc.gov/flu/avianflu/spotlights/2023-2024/ferret-study-results.htm

  • The A(H5N1) virus from the human case in Texas spread efficiently between ferrets in direct contact but did not spread efficiently between ferrets via respiratory droplets
  • reinforce the need for people who have exposure to infected animals to take precautions 
  • No changes to risk assessment

Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Viruses in U.S. Dairy Cattle and Detection of Two Human Cases – United States, 2024
https://pubmed.ncbi.nlm.nih.gov/38814843/

2024 Highly pathogenic avian influenza (H5N1) – Michigan Dairy Herd and Poultry Flock Summary
https://www.aphis.usda.gov/sites/default/files/hpai-h5n1-dairy-cattle-mi-epi-invest.pdf
“Based on the epidemiological findings, the majority of links between affected dairy premises, and between dairy and poultry premises, are indirect from shared people, vehicles, and equipment.”

Highly Pathogenic Avian Influenza H5N1 Genotype B3.13 in Dairy Cattle: National Epidemiologic Brief https://www.aphis.usda.gov/sites/default/files/hpai-dairy-national-epi-brief.pdf

Canadians have updated (4 June) their milking pre-print. I expect there will be rolling updates. 
Longitudinal Influenza A Virus Screening of Retail Milk from Canadian Provinces (Rolling Updates)
https://www.medrxiv.org/content/10.1101/2024.05.28.24308052v2

Does pasteurization inactivate bird flu virus in milk?
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2364732
Evaluation of thermal stability of HPAI H5N1, human H3N2 virus, H1, H3, H7, H9, H10. avian H3 virus = highest , HPAI = moderate thermal stability. standard pasteurization methods = effective.

Pasteurisation temperatures effectively inactivate influenza A viruses in milk
https://www.medrxiv.org/content/10.1101/2024.05.30.24308212v1
Pasteurisation effective for inactivation of human + avian influenza, influenza D, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins. infectivity rapidly lost + undetectable before recommended pasteurisation time.

Cross-Species Transmission of Highly Pathogenic Avian Influenza (HPAI) H5N1 Virus in the U.S. Dairy Cattle: A Comprehensive Review
https://www.preprints.org/manuscript/202405.2137/v1
Yet another review of current epidemiological landscape of HPAI H5N1 in U.S. dairy cows and the recent interspecies transmission events of HPAI H5N1 in other mammals reported in other countries.

Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Viruses in U.S. Dairy Cattle and Detection of Two Human Cases — United States, 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7321e1.htm

Cow’s Milk Containing Avian Influenza A(H5N1) Virus — Heat Inactivation and Infectivity in Mice
https://www.nejm.org/doi/full/10.1056/NEJMc2405495
Milk samples from HPAI H5 affected herd in New Mexico, viruses isolated. Heat treatment at 63°C reduced virus titers below the detection limit. HPAI remain infectious for several weeks in raw milk kept at 4°C. Infected mice had disease at 1dpi.

The mammary glands of cows abundantly display receptors for circulating avian H5 viruses
https://www.biorxiv.org/content/10.1101/2024.05.24.595667v3
2344b HPAI H5 from cattle bind significantly in the mammary gland, whereas classical H5 proteins failed to do so.  9-O-acetyl modification prominent in all tissues , 5-N-glycolyl modification is not. receptors are available in the lungs, and lower respiratory tract infections are often not efficiently transmitted and cause severe disease.

Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm
https://www.researchsquare.com/article/rs-4422494/v1
Isolation of HPAI H5N1 from environmental swab samples from a dairy farm in Kansas. Two distinctive mutations in the PB2 (E249G) and NS1 (R21Q) genes, 1.7% of reads w PB2 E627K. PB2 and NS most closely related to human case.

Longitudinal Influenza A Virus Screening of Retail Milk from Canadian Provinces (Rolling Updates)
https://www.medrxiv.org/content/10.1101/2024.05.28.24308052v1
Pan-Canadian Milk (PCM) Network: 8 retail milk samples from Canada (NL, NB, QC, MB, and AB) and all have tested negative for influenza A virus RNA. Routine surveillance of retail milk = cost-effective, standardized, scalable and easily accessible manner.

From birds to mammals: spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle led to efficient intra- and interspecies transmission
https://www.biorxiv.org/content/10.1101/2024.05.22.595317v1
Brilliant paper addressing key questions in cattle HPAI. 3-20% cattle affected, disease 5-14 days. More shedding in clinical cattle. Staining of tissues = tropism  for the epithelial cells lining the alveoli of the mammary gland. Genomic analysis reveals multidirectional interspecies transmissions. And they have mapped how virus spread between farms. This paper is worth the time. 

Avian Influenza Virus (H5N1) Was Not Detected Among Dairy Cattle and Farm Workers in Pakistan
https://onlinelibrary.wiley.com/doi/full/10.1111/irv.13317
HPAI not detected in dairy cattle and farm workers in Pakistan. Samples originally collected for influenza D work. Some previous testing also in Canada and Germany, negative. Seems that infection in dairy cows localised to US (for now)

Detection of Hemagglutinin H5 Influenza A Virus Sequence in Municipal Wastewater Solids at Wastewater Treatment Plants with Increases in Influenza A in Spring, 2024
https://pubs.acs.org/doi/10.1021/acs.estlett.4c00331
Monitoring of 190 wastewater treatment plants across US  ???? IAV RNA concentrations at 59 in spring 2024. Specific H5 testing showed increase due to H5 in 4 tested, all which catch discarded animal waste.

Characterization of highly pathogenic avian influenza virus in retail dairy products in the US
https://www.medrxiv.org/content/10.1101/2024.05.21.24307706v1
297 samples of Grade A pasteurised retail milk products (23 types) collected from 17 US states over 132 processors in 38 states. 20.2% positive by qPCR, all neg by egg innocs.

Influenza H5N1 and H1N1 viruses remain infectious in unpasteurized milk on milking machinery surfaces
https://www.medrxiv.org/content/10.1101/2024.05.22.24307745v1
HPAI H5N1 and H1N1 spiked into milk and put onto surfaces. HPAI remained infectious on surfaces for more than an hour = unpasteurized milk containing the H5N1 virus will remain infectious on milking equipment.

Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities.
https://www.medrxiv.org/content/10.1101/2024.05.10.24307179v1
19 of 23 monitored sites had at least one detection event, and the H5N1 serotype became dominant over seasonal influenza over time. 

Preliminary report on genomic epidemiology of the 2024 H5N1 influenza A virus outbreak in U.S. cattle 
(Part 1 of 2)
https://virological.org/t/preliminary-report-on-genomic-epidemiology-of-the-2024-h5n1-influenza-a-virus-outbreak-in-u-s-cattle-part-1-of-2/970?s=03
(Part 2 of 2)
https://virological.org/t/preliminary-report-on-genomic-epidemiology-of-the-2024-h5n1-influenza-a-virus-outbreak-in-u-s-cattle-part-2-of-2/971
This comprises the summary of genetic analysis of the sequences generated by USDA undertaken by evolutionary biologists. Highlights features such as reassortment prior to entering cattle, a single point of introduction into cattle, estimated date of virus introduction into the cattle population, mostly likely to have originated in Texas, and the presence of potentially adaptive mutations in cattle. 

The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland
https://www.biorxiv.org/content/10.1101/2024.05.03.592326v1
Turns out that cattle have avian type receptors in their mammary glands, which may explain why this is the “preferred” site of replication in cattle, and why there havent been to many occurences of the PB2 mutation in the cattle sequences. 

Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker
https://www.nejm.org/doi/full/10.1056/NEJMc2405371
Description of human case

Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024
https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article
Infected cattle experienced nonspecific illness, reduced feed intake and rumination, and an abrupt drop in milk production, but fatal systemic influenza infection developed in domestic cats fed raw (unpasteurized) colostrum and milk from affected cows.

Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle
https://www.biorxiv.org/content/10.1101/2024.05.01.591751v1
Great to see the analysis by the USDA and folks involved in the cattle outbreaks. Genomic analysis and epidemiological investigation showed a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode.. 

Potential Pathways of Spread of Highly Pathogenic Avian Influenza A/H5N1 Clade 2.3.4.4b Across Dairy Farms in the United States
https://www.medrxiv.org/content/10.1101/2024.05.02.24306785v1
Led by folks at the Kirby using spatial models to understand how spread may have occurred. Assumes that spread is occurring in real time.. Rather than identification of cases as more testing has been done.

Experimental Infection of Cattle with Highly Pathogenic Avian Influenza Virus (H5N1)
https://wwwnc.cdc.gov/eid/article/14/7/07-1468_article
4 calves experimentally infected with HPAI H5 (2006 strain). All remained healthy with no clinical signs. Limited shedding in nasal swabs, but shed low amounts of virus at 1dpi, 2dpi. All seroconverted.

Further Experiments Relating to the Propagation of Virus in the Bovine Mammary Gland
https://pubmed.ncbi.nlm.nih.gov/17648631/
From 1953: Human influenza type persisted
in the mammary gland for ~ 2 weeks, titres rose in milk and persisted for several days, neutralizing antibodies
detected soon after the virus had disappeared.

Studies relating to the formation of neutralizing antibody following the propagation of influenza and Newcastle disease virus in the bovine mammary gland
https://pubmed.ncbi.nlm.nih.gov/13316626/
A follow up, in 1955, w PR8 (these days a laboratory strain) (in goats as a sub for cattle). Infection in the mammary glad. Removal of mammary glad = decrease in antibody content in blood = neutralising antibodies being produced in mammary glad.

Significant rising antibody titres to influenza A are associated with an acute reduction in milk yield in cattle
https://sciencedirect.com/science/article/pii/S1090023307002419
Sporadic cases of “milk drop” investigated in a Holstein Friesian dairy herd in Devon, with increased antibody titres against human H3N2 and H1N1 associated with an acute fall in milk production

Influenza A in Bovine Species: A Narrative Literature Review
https://mdpi.com/1999-4915/11/6/561
There is a long history of influenza A in cattle. First case is 1949 with 160,000 cattle affected in Japan. Generally mammalian H1 and H3 subtypes implicated.

Influenza D virus
https://doi.org/10.1016/j.coviro.2020.08.004
Cattle are, of course, the central reservoir for influenza D viruses (a different virus species). Lots of scope for interesting work still to be done on influenza viruses in cattle.