The genetics of highly pathogenic avian influenza viruses of subtype H5 in Germany, 2006-2020

The H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage emerged in China in 1996. Rooted in the respective gs/GD lineage, the hemagglutinin (HA) gene of highly pathogenic avian influenza viruses (HPAIV) has genetically diversified into a plethora of clades and subclades and evolved into an assortment of sub- and genotypes. Some caused substantial losses in the poultry industry and had a major impact on wild bird populations alongside public health implications due to a zoonotic potential of certain clades. After the primary introduction of the HPAI H5N1 gs/GD lineage into Europe in autumn 2005 and winter 2005/2006, Germany has seen recurring incursions of four varying H5Nx subtypes (H5N1, H5N8, H5N5, H5N6) carrying multiple distinct reassortants, all descendants of the gs/GD virus. The first HPAIV H5 epidemic in Germany during 2006/2007 was caused by a clade 2.2 subtype H5N1 virus. Phylogenetic analysis confirmed three distinct clusters belonging to clades 2.2.1, 2.2.2 and 2.2, concurring with geographic and temporal structures. From 2014 onwards, HPAIV clade 2.3.4.4 has dominated the epidemiological situation in Germany. The initial clade 2.3.4.4a HPAIV H5N8, reaching Germany in November 2014, caused a limited epidemic affecting five poultry holdings, one zoo in Northern Germany and few wild birds. After November 2016, HPAIV of clade 2.3.4.4b have dominated the situation to date. The most extensive HPAIV H5 epidemic on record reached Germany in winter 2016/2017, encompassing multiple incursion events with two subtypes (H5N8, H5N5) and entailing five reassortants. A novel H5N6 clade 2.3.4.4b strain affected Germany from December 2017 onwards, instigating low-level infection in smallholdings and wild birds. Recently, in spring 2020, a novel incursion of a genetically distinct HPAI clade 2.3.4.4b H5N8 virus caused another epidemic in Europe, which affected a small number of poultry holdings, one zoo and two wild birds throughout Germany.