OmniVira

Literature detail

The haemagglutinin gene of bovine-origin H5N1 influenza viruses currently retains receptor-binding and pH-fusion characteristics of avian host phenotype.

Jiayun Yang1 Mehnaz Qureshi1 Reddy Kolli1 Thomas P Peacock1,2 Jean-Remy Sadeyen1 Toby Carter1 Samuel Richardson1 Rebecca Daines1 Wendy S Barclay2 Ian H Brown1 Munir Iqbal1
Affiliations 2 institutions
  1. The Pirbright Institute, Pirbright, UK.
  2. Department of Infectious Disease, Imperial College London, London, UK.
PMID 39803980 2025 Emerg Microbes Infect eng ppublish
PubMed DOI Browse context

Article

Publication summary

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has caused a panzootic affecting all continents except Australia, expanding its host range to several mammalian species. In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. Over 891 dairy farms across 16 states have tested positive until 25 December 2024, with zoonotic infections reported among dairy workers. This raises concerns about the virus undergoing evolutionary changes in cattle that could enhance its zoonotic potential. The Influenza glycoprotein haemagglutinin (HA) facilitates entry into host cells through receptor binding and pH-induced fusion with cellular membranes. Adaptive changes in HA modulate virus-host cell interactions. This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom, focusing on receptor binding, pH fusion, and thermostability. All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility (pH 5.0-5.5). We further investigated the impact of emerging HA substitutions seen in the ongoing cattle outbreaks, but saw little phenotypic difference, with continued exclusive binding to avian-like receptor analogues and pHs of fusion above 5.8. This suggests that the HA genes from the cattle and goat outbreaks do not pose an enhanced threat compared to circulating avian viruses. However, given the rapid evolution of H5 viruses, continuous monitoring and updated risk assessments remain essential to understanding virus zoonotic and pandemic risks.

cattle and goat H5N1 High pathogenicity avian influenza pH fusion receptor binding zoonotic risk Hemagglutinin Glycoproteins, Influenza Virus Influenza A Virus, H5N1 Subtype Orthomyxoviridae Infections Animals Birds Cattle Goats Humans Hydrogen-Ion Concentration Influenza in Birds Influenza, Human Phenotype Phylogeny

Structured evidence records

Evidence records

7 total
Cross Species Transmission 2 records
Cross Species Transmission Extraction confidence 0.90
Key finding

Clade 2.3.4.4b avian-origin H5N1 virus infected dairy cattle and goats, demonstrating cross-species transmission from birds to livestock.

Virus
IAV H5N1
Location
United States United States
Supporting text

In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1, indicating the viruses of avian origin infected these mammalian livestock.

Method
genetic comparison; receptor binding assay; pH fusion assay
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Geographic raw
United States
Country inferred
United States
Cross Species Transmission Extraction confidence 0.90
Key finding

Avian-origin clade 2.3.4.4b H5N1 virus infected goats, indicating cross-species transmission from birds to mammalian livestock.

Virus
IAV H5N1
Location
United States United States
Supporting text

In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. This indicates avian-origin H5N1 virus transmission into goats.

Method
genetic comparison; receptor binding assay; pH fusion assay
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Geographic raw
United States
Country inferred
United States
Genomic Evolution 2 records
Genomic Evolution Extraction confidence 0.80
Key finding

The HA genes from bovine- and goat-origin H5N1 clade 2.3.4.4b viruses were genetically compared to avian strains, showing retention of avian-like receptor-binding features without adaptive shift toward mammalian or human-type receptor preference.

Virus
IAV H5N1
Host
Bos taurus
Location
Not specified
Supporting text

This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom… MeSH terms include 'Influenza A Virus, H5N1 Subtype / genetics' and 'Phylogeny'.

Genes or proteins
haemagglutinin gene; HA
Analysis methods
genetic comparison; phylogenetic analysis
Genomic Evolution Extraction confidence 0.80
Key finding

The HA genes from goat-origin H5N1 viruses were genetically compared to avian clade 2.3.4.4b strains, demonstrating conservation of avian-like receptor binding and fusion characteristics.

Virus
IAV H5N1
Location
Not specified
Supporting text

This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom… MeSH terms include 'Influenza A Virus, H5N1 Subtype / genetics' and 'Phylogeny'.

Genes or proteins
haemagglutinin gene; HA
Analysis methods
genetic comparison; phylogenetic analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.85
Key finding

The haemagglutinin (HA) of bovine- and goat-origin H5N1 viruses retains avian-like receptor binding and pH fusion features, showing no molecular adaptation toward mammalian receptor usage.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility.

Genes or proteins
haemagglutinin; HA
Receptors
avian-like receptors
Mechanism types
receptor_binding; cell_entry; pH_fusion
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

Cattle and goat H5N1 influenza viruses exhibited exclusive binding to avian-like receptors and retained avian-type pH fusion properties, indicating no adaptation toward mammalian receptor usage.

Virus
IAV H5N1
Location
Not specified
Supporting text

All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility (pH 5.0–5.5). We further investigated the impact of emerging HA substitutions seen in the ongoing cattle outbreaks, but saw little phenotypic difference, with continued exclusive binding to avian-like receptor analogues and pHs of fusion above 5.8.

Method
receptor binding assay; pH fusion assay
Receptors
avian-like receptors
Spillover Event 1 records
Spillover Event Extraction confidence 0.95
Key finding

Zoonotic infections among dairy workers indicate animal-to-human transmission of bovine-origin H5N1 influenza virus in the United States.

Virus
IAV H5N1
Location
United States United States
Supporting text

In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. Over 891 dairy farms across 16 states have tested positive until 25 December 2024, with zoonotic infections reported among dairy workers.

Study design
outbreak investigation
Transmission direction
animal-to-human
Geographic raw
United States
Country inferred
United States