OmniVira

Pathogenicity and transmissibility of bovine H5N1 influenza virus.

Amie J Eisfeld1 Asim Biswas1 Lizheng Guan1 Chunyang Gu1 Tadashi Maemura1 Sanja Trifkovic1 Tong Wang1 Lavanya Babujee1 Randall Dahn1 Peter J Halfmann1 Tera Barnhardt2 Gabriele Neumann1 Yasuo Suzuki3 Alexis Thompson4 Amy K Swinford5 Kiril M Dimitrov5 Keith Poulsen6 Yoshihiro Kawaoka7,8,9,10
Affiliations 10 institutions
  1. Influenza Research Institute, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
  2. Heritage Vet Partners, Johnson, KS, USA.
  3. Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  4. Texas A&M Veterinary Medical Diagnostic Laboratory, Canyon, TX, USA.
  5. Texas A&M Veterinary Medical Diagnostic Laboratory, College Station, TX, USA.
  6. Wisconsin Veterinary Diagnostic Laboratory, University of Wisconsin-Madison, Madison, WI, USA.
  7. Influenza Research Institute, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA. [email protected].
  8. Department of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. [email protected].
  9. The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, Japan. [email protected].
  10. The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan. [email protected].
PMID38977017 DOI10.1038/s41586-024-07766-6 Year2024 Journal Nature Languageeng Statusppublish

Abstract

Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. In the spring of 2024, an unprecedented outbreak of HPAI H5N1 in bovine herds occurred in the USA, with virus spread within and between herds, infections in poultry and cats, and spillover into humans, collectively indicating an increased public health risk1-4. Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species, however, this tropism was also observed for an older HPAI H5N1 virus isolate. Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals.

Supporting text Virus Host Location
Cattle Diseases 47 Influenza A Virus, H5N1 Subtype 300 Orthomyxoviridae Infections 228 Virulence 108 Animals 1948 Cattle 126 Female 289 Ferrets 79 Humans 1440 Influenza, Human 286 Laryngeal Masks 1 Mammary Glands, Animal 4 Mice 253 Mice, Inbred BALB C 73 Milk 14 Seroconversion 7 Sialic Acids 29 United States 46 Viral Tropism 45 Viral Zoonoses 65

Evidence records

6 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Virus Isolation
1 records
OVE8190 Virus Isolation
Key finding

An infectious HPAI H5N1 virus was isolated from milk of infected cows during the 2024 outbreak.

Virus
Influenza A virus H5N1
Host
domestic cattle Bos taurus Natural host
Location
Not specified
Supporting text

Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets.

Sample type
milk
Transmission Evidence
1 records · 1 evidence types
Evidence type Outbreak Investigation
1 records
OVE8196 Outbreak Investigation
Key finding

An unprecedented outbreak of highly pathogenic avian influenza H5N1 occurred in bovine herds in the USA in spring 2024, with documented spread within and between herds, infections in poultry and cats, and detected spillover into humans.

Virus
Influenza A virus H5N1
Host
birds Aves Natural host domestic cat Felis catus Natural host human Homo sapiens Natural host domestic cattle Bos taurus Natural host
Location
United States
Supporting text

In the spring of 2024, an unprecedented outbreak of HPAI H5N1 in bovine herds occurred in the USA, with virus spread within and between herds, infections in poultry and cats, and spillover into humans.

Method
field outbreak investigation | epidemiological documentation | virus detection in infected cow milk
Transmission direction
cross-species transmission
Geographic raw
USA
Country inferred
USA
Outbreak setting
bovine herds
Outbreak time
spring of 2024
Outbreak scale
unprecedented outbreak involving multiple herds and species
Experimental Infection
3 records · 2 evidence types
Evidence type Pathogenicity Experiment
2 records
OVE8191 Pathogenicity Experiment
Key finding

Experimental infection of mice with the bovine H5N1 virus resulted in systemic viral spread including to the mammary glands.

Virus
Influenza A virus H5N1
Host
house mouse Mus musculus Experimental system
Location
Not specified
Supporting text

Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species.

Method
experimental infection | virus detection in organs
Experimental system
mouse experimental infection model
OVE8192 Pathogenicity Experiment
Key finding

Experimental infection of ferrets with the bovine H5N1 virus caused systemic spread including infection of mammary glands.

Virus
Influenza A virus H5N1
Host
domestic ferret Mustela putorius furo Experimental system
Location
Not specified
Supporting text

Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species.

Method
experimental infection | virus detection in organs
Experimental system
ferret experimental infection model
Evidence type Host Range Experiment
1 records
OVE8194 Host Range Experiment
Key finding

Bovine HPAI H5N1 virus showed limited susceptibility and inefficient infection in ferrets, with only one of four exposed ferrets seroconverting without detectable virus replication.

Virus
Influenza A virus H5N1
Host
domestic ferret Mustela putorius furo Experimental system domestic cattle Bos taurus Natural host
Location
Not specified
Supporting text

Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection).

Method
animal challenge | serological testing | virus detection assay
Sample type
serum
Experimental system
animal exposure model (ferrets experimentally exposed to bovine H5N1 virus)
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE8193 Receptor Usage
Key finding

Bovine HPAI H5N1 virus binds to sialic acids expressed in human upper airways, indicating receptor compatibility with human airway receptors.

Virus
Influenza A virus H5N1
Host
human Homo sapiens Experimental system
Location
Not specified
Supporting text

Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways.

Method
receptor-binding assay
Receptors
sialic acids