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Influenza Other Respir Viruses.H5N1 Clade 2.3.4.4b Infections in Domestic Cats During an Avian Influenza Outbreak in Italy:Implications for One Health

tetano

Editor, Senior Moderator
Influenza Other Respir Viruses

. 2026 Sep;20(9):e70311.
doi: 10.1111/irv.70311.

H5N1 Clade 2.3.4.4b Infections in Domestic Cats During an Avian Influenza Outbreak in Italy: Implications for One Health Surveillance​


Giulia D'Annunzio 1 , Ana Moreno 1 , Giovanni Tosi 1 , Patrizia Bassi 1 , Alessio Bortolami 2 , Giuseppe Diegoli 3 , Alessandra Drago 2 , Alice Fusaro 2 , Luca Gelmini 1 , Lucia Rita Gibelli 1 , Tiziana Lazzarotto 4 5 , Elisabetta Lilliu 1 , Luisa Loli Piccolomini 3 , Andrea Maroni 6 , Enrica Martini 7 , Giulio Matteo 3 , Giovanna Mattei 3 , Luisa Vera Muscatello 8 , Isabella Monne 2 , Elisa Palumbo 2 , Giorgia Prezzemolo 7 , Valentina Ravaioli 1 , Davide Resi 7 , Luigi Ruocco 6 , Michele Ottavio Sabatino 7 , Enrico Savegnago 2 , Marco Sordilli 6 , Calogero Terregino 2 , Clara Tolini 1 , Giuseppe Merialdi 1

Affiliations


Abstract​


Background: H5Nx goose/Guangdong (Gs/GD) lineage highly pathogenic avian influenza (HPAI) viruses pose a significant public health threat due to their global spread, mutation accumulation, and expanding host range. The descendant clade 2.3.4.4b has been causing widespread infections in birds and increasing spillover events in mammals.


Methods: This report documents the first fatal case of highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b infection in a domestic cat in Italy, detected in early January 2025. The cat (CAT 1) resided on a backyard poultry farm experiencing a high pathogenicity avian influenza outbreak and succumbed rapidly following the onset of respiratory signs. A second exposed cat (CAT 2) developed clinical disease without fatal outcome. Comprehensive outbreak investigations were conducted, including pathological, serological, molecular analyses, and genomic characterization.


Results: Pathological examination of CAT 1 revealed acute necrotizing bronchointerstitial pneumonia, non-suppurative meningoencephalitis, and disseminated foci of hepatic necrosis. Interestingly, the PB2-E627K mutation associated with mammalian virus adaptation was observed in the feline viral isolate compared to avian isolates. Such polymerase complex mutations are key determinants of host range and increase pathogenicity in mammals. CAT 2 from the same farm tested negative for AIV genome detection but subsequently seroconverted for antibodies against NPA, H5, and N1.


Conclusion: Sharing these findings is crucial for surveillance aimed at enabling early identification of increased risks to human and animal health, preventing cross-species viral transmission and mitigating the risk of potential spillover events.

Keywords: HPAIV H5N1 clade 2.3.4.4b; Italy; PB2‐E627K mutation; cat.
 
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