OmniVira

Literature detail

H5N1 clade 2.3.4.4b dynamics in experimentally infected calves and cows.

Nico Joel Halwe1 Konner Cool2 Angele Breithaupt3 Jacob Schön1 Jessie D Trujillo2 Mohammed Nooruzzaman4 Taeyong Kwon2 Ann Kathrin Ahrens1 Tobias Britzke3 Chester D McDowell2 Ronja Piesche1 Gagandeep Singh2 Vinicius Pinho Dos Reis1 Sujan Kafle2 Anne Pohlmann1 Natasha N Gaudreault2 Björn Corleis5 Franco Matias Ferreyra6 Mariano Carossino7,8 Udeni B R Balasuriya7,8 Lisa Hensley9 Igor Morozov2 Lina M Covaleda4 Diego G Diel4 Lorenz Ulrich1 Donata Hoffmann1 Martin Beer10 Juergen A Richt11
Affiliations 11 institutions
  1. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  2. Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
  3. Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  4. Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  5. Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
  6. Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
  7. Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
  8. Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
  9. Zoonotic and Emerging Disease Research Unit, National Bio and Agro-Defense Facility, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS, USA.
  10. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany. [email protected].
  11. Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. [email protected].
PMID 39321846 2025 Nature eng ppublish
PubMed DOI Browse context

Article

Publication summary

In March 2024, highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b H5N1 infections were reported in dairy cows in Texas, USA<sup>1</sup>. Rapid dissemination to more than 380 farms in 14 states followed<sup>2</sup>. Here we provide results of two independent clade 2.3.4.4b experimental infection studies evaluating the oronasal susceptibility to and transmission of a US H5N1 bovine isolate, genotype B3.13 (H5N1 B3.13), in calves, and the susceptibility of lactating cows following direct mammary gland inoculation of either H5N1 B3.13 or a current EU H5N1 wild bird isolate, genotype euDG (H5N1 euDG). Inoculation of the calves resulted in moderate nasal replication and shedding with no severe clinical signs or transmission to sentinel calves. In dairy cows, infection resulted in no nasal shedding, but severe acute infection of the mammary gland with necrotizing mastitis and high fever was observed for both H5N1 isolates. Milk production was rapidly and markedly reduced and the physical condition of the cows was severely compromised. Virus titres in milk rapidly peaked at 10<sup>9</sup> 50% tissue culture infectious dose (TCID<sub>50</sub>) per ml, but systemic infection did not ensue. Notably, the adaptive mutation E627K emerged in the viral polymerase basic protein 2 (PB2) after intramammary replication of H5N1 euDG. Our data suggest that in addition to H5N1 B3.13, other HPAIV H5N1 strains have the potential to replicate in the udder of cows and that milk and milking procedures, rather than respiratory spread, are likely to be the primary routes of H5N1 transmission between cattle.

Cattle Diseases Influenza A Virus, H5N1 Subtype Orthomyxoviridae Infections Animals Cattle Disease Susceptibility Female Genotype Lactation Mammary Glands, Animal Milk Nose Texas Virus Replication Virus Shedding

Structured evidence records

Evidence records

5 total
Host Range Experiment 3 records
Host Range Experiment Extraction confidence 1.00
Key finding

Calves experimentally infected oronasally with H5N1 B3.13 showed moderate nasal replication and shedding but no transmission to sentinel calves.

Virus
IAV H5N1
Location
Not specified
Supporting text

Two independent clade 2.3.4.4b experimental infection studies evaluated the oronasal susceptibility and transmission of a US H5N1 bovine isolate, genotype B3.13 (H5N1 B3.13), in calves. Inoculation resulted in moderate nasal replication and shedding with no severe clinical signs or transmission to sentinel calves.

Method
experimental infection; oronasal inoculation
Sample type
nasal samples
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

Lactating cows directly inoculated in the mammary gland with either H5N1 B3.13 or H5N1 euDG developed severe intramammary infection with high virus titers in milk and necrotizing mastitis but no nasal shedding.

Virus
IAV H5N1
Location
Not specified
Supporting text

In dairy cows, infection resulted in no nasal shedding, but severe acute infection of the mammary gland with necrotizing mastitis and high fever was observed for both H5N1 isolates (H5N1 B3.13 and H5N1 euDG). Milk production was rapidly and markedly reduced and virus titres in milk rapidly peaked at 10^9 TCID50 per ml.

Method
experimental infection; direct mammary gland inoculation
Sample type
milk; mammary gland
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

H5N1 euDG replicated efficiently in the mammary gland of lactating cows, where the adaptive mutation E627K emerged in PB2 during intramammary replication.

Virus
IAV H5N1
Location
Not specified
Supporting text

In dairy cows, infection resulted in no nasal shedding, but severe acute infection of the mammary gland with necrotizing mastitis and high fever was observed for both H5N1 isolates (H5N1 B3.13 and H5N1 euDG). Notably, the adaptive mutation E627K emerged in the viral polymerase basic protein 2 (PB2) after intramammary replication of H5N1 euDG.

Method
experimental infection; direct mammary gland inoculation
Sample type
milk; mammary gland
Experimental system
in vivo animal experiment
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

A wild bird-derived H5N1 euDG isolate successfully infected dairy cows after intramammary inoculation, demonstrating avian-to-bovine cross-species transmission.

Virus
IAV H5N1
Location
EU
Supporting text

The study evaluated susceptibility of lactating cows following direct mammary gland inoculation of either H5N1 B3.13 or a current EU H5N1 wild bird isolate, genotype euDG, showing that both caused infection in cattle.

Method
experimental infection
Study design
animal experiment
Transmission direction
animal-to-animal
Geographic raw
EU
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The PB2 E627K mutation appeared during intramammary replication of the H5N1 euDG strain in cows, suggesting mammalian adaptation.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Notably, the adaptive mutation E627K emerged in the viral polymerase basic protein 2 (PB2) after intramammary replication of H5N1 euDG.

Genes or proteins
PB2
Mutations
E627K
Mechanism types
polymerase_activity; host_adaptation