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

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

Anthony V Signore  1 , Tomy Joseph  2 , Charlene Ranadheera  3 , Cassidy N G Erdelyan  1 , Tamiru N Alkie  1 , Sugandha Raj  1 , Lemarie Pama  1 , Ifeoluwa Ayilara  1 , Tamiko Hisanaga  1 , Oliver Lung  1 , Nathalie Bastien  3 , Yohannes Berhane  1   4   5   6
Affiliations

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

Anthony V Signore et al. Emerg Microbes Infect. 2025 Dec.

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.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
(A) Maximum likelihood phylogenetic trees inferred with HA (left) and NA (right) gene sequences. Clade labels represent HA and NA subtypes, with an asterisk (*) denoting H11 isolates. Trees are coloured according to isolate pathogenicity. (B) Time-scaled phylogenetic tree based on whole-genome sequences of D1.1 outbreak isolates collected from poultry farms in the Frasier Valley of British Columbia, Canada between October 21 and November 17, 2024. Tree branches are coloured according to the presence or absence of the oseltamivir resistance marker NA: H275Y. (C) Half-maximal inhibitory concentration (IC50) of oseltamivir, peramivir, and zanamivir against an NA-H275Y outbreak variant (A/Chicken/BC/FAV-0289-3/2024) relative to resistant and sensitive controls.
See this image and copyright information in PMC

References

    1. Engelsma M, Heutink R, Harders F, et al. . Multiple introductions of reassorted highly pathogenic avian influenza: H5Nx viruses clade 2.3.4.4b causing outbreaks in wild birds and poultry in The Netherlands, 2020–2021. Microbiol Spectr. 2022 Apr 27;10(2):e0249921. - PMC - PubMed
    1. Gass JD, Dusek RJ, Hall JS, et al. . Global dissemination of influenza A virus is driven by wild bird migration through Arctic and subarctic zones. Mol Ecol. 2023 2023-01-01;32(1):198–213. - PMC - PubMed
    1. Caliendo V, Lewis NS, Pohlmann A, et al. . Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021. Sci Rep. 2022 2022-07-11;12(1):11729. - PMC - PubMed
    1. Alkie TN, Lopes S, Hisanaga T, et al. . A threat from both sides: multiple introductions of genetically distinct H5 HPAI viruses into Canada via both East Asia-Australasia/Pacific and Atlantic flyways. Virus Evol. 2022;8(2):veac077. doi:10.1093/ve/veac077 - DOI - PMC - PubMed
    1. Giacinti JA, Signore AV, Jones MEB, et al. . Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021–2022. mBio. 2024 Aug 14;15(8):e0320323. doi:10.1128/mbio.03203-23 - DOI - PMC - PubMed

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