Neuraminidase reassortment and oseltamivir resistance in clade 2.3.4.4b A(H5N1) viruses circulating among Canadian poultry, 2024

Anthony V Signore; Tomy Joseph; Charlene Ranadheera; Cassidy N G Erdelyan; Tamiru N Alkie; Sugandha Raj; Lemarie Pama; Ifeoluwa Ayilara; Tamiko Hisanaga; Oliver Lung; Nathalie Bastien; Yohannes Berhane

doi:10.1080/22221751.2025.2469643

Neuraminidase reassortment and oseltamivir resistance in clade 2.3.4.4b A(H5N1) viruses circulating among Canadian poultry, 2024

Emerg Microbes Infect. 2025 Dec;14(1):2469643. doi: 10.1080/22221751.2025.2469643. Epub 2025 Mar 11.

Authors

Affiliations

¹ National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Canada.
² Animal Health Centre, BC Ministry of Agriculture and Food, Abbotsford, Canada.
³ National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
⁴ Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
⁵ Department of Animal Science, University of Manitoba, Winnipeg, Canada.
⁶ Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.

Abstract

We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada. Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir. We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses.

Keywords: A(H5N1); H5 clade 2.3.4.4b; NA-H275Y; oseltamivir resistance; reassortment.

MeSH terms

Animals
Antiviral Agents* / pharmacology
British Columbia / epidemiology
Canada / epidemiology
Chickens / virology
Disease Outbreaks / veterinary
Drug Resistance, Viral* / genetics
Influenza A Virus, H5N1 Subtype* / drug effects
Influenza A Virus, H5N1 Subtype* / genetics
Influenza A Virus, H5N1 Subtype* / isolation & purification
Influenza in Birds* / epidemiology
Influenza in Birds* / virology
Mutation
Neuraminidase* / genetics
Oseltamivir* / pharmacology
Phylogeny
Poultry Diseases / epidemiology
Poultry Diseases / virology
Poultry* / virology
Reassortant Viruses* / drug effects
Reassortant Viruses* / genetics
Viral Proteins / genetics

Substances

Neuraminidase
Oseltamivir
Antiviral Agents
Viral Proteins
NA protein, influenza A virus

Grants and funding

This work was supported by Canadian Food Inspection Agency: [HPAI Emergency Funding]; Defence Research and Development Canada: [Grant Number CW2248375 – 39903-23076 CSSP 2541].