Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. Viruses from these two principal sources can be distinguished by their hemagglutinin genes, which segregate into two distinct sublineages (termed B1 and B2) within clade 2.3.4.4b, as well as their different internal gene compositions. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe.

Agence Nationale de Sécurité Sanitaire de l'Alimentation de l'Environnement et du Travail Laboratoire de Ploufragan Plouzané Niort Unité de Virologie Immunologie Parasitologie Avaires et Cunicoles Ploufragan France

Animal and Plant Health Agencygrid 422685 f Weybridge New Haw Addlestone Surrey United Kingdom

Croatian Veterinary Institute Poultry Centre Zagreb Croatia

Department for Virus and Microbiological Special Diagnostics Statens Serum Institut Copenhagen Denmark

Department of Microbiology National Veterinary Institute SVA Uppsala Sweden

Department of Pathobiology and Population Sciences Royal Veterinary Collegegrid 20931 39 Hatfield United Kingdom

Department of Pathology National Veterinary Institute SVA Uppsala Sweden

Department of Poultry Diseases National Veterinary Research Institute Puławy Poland

Department of Veterinary and Animal Sciences University of Copenhagen Frederiksberg Denmark

European Union Reference Laboratory for Avian Influenza and Newcastle Disease Istituto Zooprofilattico Sperimentale delle Veneziegrid 419593 3 Legnaro Padua Italy

Institute of Diagnostic Virology Friedrich Loeffler Institute Greifswald Insel Riems Germany

OIE FAO International Reference Laboratory for Avian Influenza Swine Influenza and Newcastle Disease Animal and Plant Health Agencygrid 422685 f Weybridge Addlestone Surrey United Kingdom

Service of Avian Virology and Immunology Sciensano Brussels Belgium

State Veterinary Institute Prague Prague Czech Republic

Wageningen Bioveterinary Research Lelystad The Netherlands

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