OmniVira

Dairy cow- and avian-origin clade 2.3.4.4b H5N1 induce severe mastitis in lactating goats and transmission to suckling goats.

Tamiru N Alkie1 Carissa Embury-Hyatt1 Anthony V Signore1 Darwin Ramos1 Estella Moffat1 Sugandha Raj1 Henok Gebrebrhan1 Ifeoluwa Ayilara1 Tamiko Hisanaga1 Cassidy N G Erdelyan1 Patrick Lloyd1 Oliver Lung1 Davor Ojkic2 Claire M Jardine3 Loren Matheson4 Darwyn Kobasa5 Zvonimir Poljak6 Samira Mubareka7,8 Richard Webby9 Yohannes Berhane10,11,12,13
Affiliations 13 institutions
  1. National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada.
  2. Animal Health Laboratory, University of Guelph, Guelph, ON, Canada.
  3. Canadian Wildlife Health Cooperative, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
  4. Centre for Security Science, Defence Research and Development Canada, Ottawa, ON, Canada.
  5. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
  6. Department of Population Medicine, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
  7. Sunnybrook Research Institute, Toronto, ON, Canada
  8. Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  9. Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
  10. National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada
  11. Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
  12. Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada
  13. Department of Pathobiology, University of Guelph, Guelph, ON, Canada. Electronic address: [email protected].
PMID40996885 DOI10.1016/j.celrep.2025.116346 Year2025 Journal Cell reports Cell Rep Languageeng Statusppublish

Abstract

The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has led to unprecedented spillover and spread among US dairy cows, raising concerns about transmission to other ruminants. We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13) or avian-H5N1 (genotype B1.2) virus. Both groups developed severe clinical mastitis and shed viruses in milk, resulting in transmission to suckling kids. Viral RNA was detected in nasal and oral swabs and various tissues, and virus-neutralizing antibodies were present in serum, milk, and bronchoalveolar lavage fluid. In vitro, both viruses replicated efficiently in goat respiratory and mammary epithelial cells. Mammary tissue expresses both α2,3- and α2,6-linked sialic acid receptors. These findings demonstrate that goats are highly susceptible to H5N1 infection, with mammary tropism facilitating transmission to offspring, and underscore the need for increased surveillance in ruminant livestock.

Supporting text Virus Host Location
CP: Microbiology 7 goats 25 influenza A(H5N1) 2 mammary glands 1 milk 14 neutralizing antibodies 5 respiratory 1 Goat Diseases 8 Influenza A Virus, H5N1 Subtype 300 Lactation 6 Mastitis 1 Orthomyxoviridae Infections 228 Animals 1948 Animals, Suckling 3 Cattle 126 Female 289 Goats 24 Mammary Glands, Animal 4 Milk 14

Evidence records

8 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Reservoir Ecology
1 records
OVE9904 Reservoir Ecology
Key finding

Goats show high susceptibility to H5N1 infection, and mammary tropism enables virus persistence and transmission to offspring, indicating potential maintenance within goat populations.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

These findings demonstrate that goats are highly susceptible to H5N1 infection, with mammary tropism facilitating transmission to offspring.

Method
in vivo infection experiment | virus detection in milk | clinical observation of mastitis
Sample type
milk | mammary tissue | nasal swabs | oral swabs
Experimental Infection
6 records · 3 evidence types
Evidence type Pathogenicity Experiment
2 records
OVE9893 Pathogenicity Experiment
Key finding

Experimental infection of lactating goats with Cow-H5N1 (genotype B3.13) caused severe clinical mastitis.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13)... Both groups developed severe clinical mastitis.

Method
controlled intramammary and respiratory inoculation | clinical observation | viral RNA detection | virological assays | serum and milk antibody detection
Experimental system
in vivo goat infection model
OVE9894 Pathogenicity Experiment
Key finding

Experimental infection of lactating goats with avian-H5N1 (genotype B1.2) caused severe clinical mastitis.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

We inoculated two groups of lactating goats via intramammary and respiratory routes with ... avian-H5N1 (genotype B1.2) virus. Both groups developed severe clinical mastitis.

Method
controlled intramammary and respiratory inoculation | clinical observation | viral RNA detection | virological assays | serum and milk antibody detection
Experimental system
in vivo goat infection model
Evidence type Host Range Experiment
2 records
OVE9901 Host Range Experiment
Key finding

Cow-H5N1 (genotype B3.13) replicated efficiently in goat respiratory and mammary epithelial cells in vitro, indicating goat cellular susceptibility.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system domestic cattle Bos taurus Experimental system
Location
Not specified
Supporting text

In vitro, both viruses replicated efficiently in goat respiratory and mammary epithelial cells.

Method
in vitro infection assay | viral replication measurement
Sample type
respiratory epithelial cells | mammary epithelial cells
Experimental system
in vitro cell culture infection
OVE9902 Host Range Experiment
Key finding

Avian-H5N1 (genotype B1.2) replicated efficiently in goat respiratory and mammary epithelial cells in vitro, confirming cross-species infectivity.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system birds Aves Experimental system
Location
Not specified
Supporting text

In vitro, both viruses replicated efficiently in goat respiratory and mammary epithelial cells.

Method
in vitro infection assay | viral replication measurement
Sample type
respiratory epithelial cells | mammary epithelial cells
Experimental system
in vitro cell culture infection
Evidence type Experimental Transmission
2 records
OVE9895 Experimental Transmission
Key finding

Cow-H5N1 (genotype B3.13) virus was experimentally transmitted from infected lactating goats to suckling kids through milk shedding under controlled conditions.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13) or avian-H5N1 (genotype B1.2) virus. Both groups developed severe clinical mastitis and shed viruses in milk, resulting in transmission to suckling kids.

Method
intramammary inoculation | virus detection in milk | viral RNA detection in recipient swabs | serological assays for neutralizing antibodies
Experimental system
animal transmission model via milk contact between infected lactating goats and suckling kids
OVE9896 Experimental Transmission
Key finding

Avian-H5N1 (genotype B1.2) virus was experimentally transmitted from infected lactating goats to suckling kids through milk shedding under controlled conditions.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13) or avian-H5N1 (genotype B1.2) virus. Both groups developed severe clinical mastitis and shed viruses in milk, resulting in transmission to suckling kids.

Method
intramammary inoculation | virus detection in milk | viral RNA detection in recipient swabs | serological assays for neutralizing antibodies
Experimental system
animal transmission model via milk contact between infected lactating goats and suckling kids
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE9903 Receptor Usage
Key finding

Goat mammary tissue expresses α2,3- and α2,6-linked sialic acid receptors linked to H5N1 host-cell tropism.

Virus
Influenza A virus H5N1
Host
goat Capra hircus Experimental system
Location
Not specified
Supporting text

Mammary tissue expresses both α2,3- and α2,6-linked sialic acid receptors. We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13) or avian-H5N1 (genotype B1.2) virus.

Method
receptor expression analysis
Receptors
α2,3-linked sialic acid receptor | α2,6-linked sialic acid receptor