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Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 7

Transmission and pathogenicity in ferrets after experimental infection with HPAI clade 2.3.4.4b H5N1 viruses Open Access

Abstract

A marked increase in the incidence of mortality amongst wild mammals attributed to infection with highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses was observed in Europe in 2021. Neurological signs and high viral antigen levels in the brain of infected wild mammals indicate that the HPAI H5N1 virus causes severe disease in mammals, but serological analysis suggests that infections may be more widespread, implying that some mammals could experience mild disease. The clinical manifestation and transmissibility of HPAI H5N1 clade 2.3.4.4b viruses amongst mammals represent critical risk factors for potential zoonotic transmission to humans. This study examined the pathogenicity, viral tissue tropism and associated pathology of three HPAI H5N1 viruses in ferrets, which are a model for influenza A infection in humans. Ferrets were experimentally infected with an HPAI H5N1 poultry virus (genotype C) and two HPAI H5N1 viruses (genotype BA) isolated from a red fox, one of which carries the zoonotic PB2-E627K mutation. The red fox isolate, but not the poultry isolate, caused high morbidity, viral shedding and mortality in ferrets. Transmission to co-housed ferrets was investigated in a group setting for the virus carrying the PB2-E627K mutation and caused neurological signs accompanied by prominent viral antigen staining in recipient ferrets compared to directly inoculated ferrets. This study shows that HPAI H5N1 clade 2.3.4.4b viruses can infect mammals with varying pathogenicity and that mammal-to-mammal transmission can occur. This increases the zoonotic potential of the virus and highlights the need for enhanced surveillance in wild mammals for early detection of potential zoonotic threats.

  • Received:
  • Accepted:
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Keyword(s): avian influenza , ferret , H5N1 , PB2-E627K and transmission
Funding
This study was supported by the:
  • Ministerie van Landbouw, Natuur en Voedselkwaliteit (Award KB-37-003-039)
    • Principal Award Recipient: NancyBeerens
  • Ministerie van Landbouw, Natuur en Voedselkwaliteit (Award WOT-01-003-096)
    • Principal Award Recipient: NancyBeerens
  • Ministerie van Landbouw, Natuur en Voedselkwaliteit (Award WOT-01-003-112)
    • Principal Award Recipient: NancyBeerens
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2025-07-08
2026-01-15

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Transmission and pathogenicity in ferrets after experimental infection with HPAI clade 2.3.4.4b H5N1 viruses
J. Gen. Virol. 106, 002124 (2025); https://doi.org/10.1099/jgv.0.002124
/content/journal/jgv/10.1099/jgv.0.002124
/content/journal/jgv/10.1099/jgv.0.002124
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