Lublin, A., Shkoda, I., Simanov, L., Hadas, R., Berkowitz, A., Lapin, K., Farnoushi, Y., Katz, R., Nagar, S., Kharboush, C., Peri Markovich, M., and King, R.
Avian Influenza (AI) has become the largest animal epidemic in the world. So far hundreds of millions birds have died or been culled due to the disease. A novel highly-pathogenic avian influenza (HPAI) subtype H5N1 virus, which emerged in 1996 in domestic geese in China, passed from wild waterfowl as a lowpathogenic (LP) virus, and in the domestic birds was modified to a High Pathogenic (HP) virus due to mutational addition of basic amino acids to the cleavage site of the Hemagglutinin (HA) protein. This "A/ goose/Guangdong/1/1996" virus killed poultry but also infected at least 18 people of whom 6 died. In 2003-6 the virus spread to Asia, Europe, Africa and the Middle East. Mass mortality of migratory birds at the Salt Qinghai Lake in West China in 2005 was a turning point in the understanding of the virus co-circulation between poultry and wild birds. Israel is situated on migratory routes for over a billion birds each year in the autumn migration from Europe to Africa and in the northwards spring migration, thus the potential for virus transmission is high. The 1996's parental virus emerged in Israel in 2006, following the Qinghai Lake event, and included meat turkeys, heavy breeders and broilers. Since then, several focal outbreaks occurred in Israel every 1-3 years. In 2012, the same AIV-H5N1 was detected in meat turkeys and found also in alley cats following consumption of the bird carcasses, with 100% identity of the HA gene. A second multi-focal outbreak of AIV-H5N1 appeared in 2015 following the worldwide wave in 2014-15. This outbreak included meat turkeys, heavy breeders and egg layers. These viruses belonged phylogenetically to clade 2.2.1.2, emerged from previous clades 2.2 and 2.2.1.1. Reassortment of viral segments of a descendant-H5 AIV of the Chinese parental virus with AIV-N8 viruses created novel H5N8 viruses, first detected in China in 2010. An 2016's variant of this virus (group-B Gochang-like, clade 2.3.4.4), was discovered in May-June 2016 in wild swans at Lake Ubsu-Nur on the Russian-Mongolian border, and reached Central Asia, Europe, Africa, Middle East and Israel. The Ubsu-Nur 2016's AIV-H5N8 was genetically identical to an AIV-H5N8 that emerged in Israel six months later during the autumn migration. This was the first H5N8 outbreak in Israel, which included meat and breeder turkeys, heavy and light breeders, layers, breeder ducks and backyard poultry, but also many wild birds, not seen in the previous H5N1 outbreaks, of at least 16 species mostly waterfowl and raptors. The cleavage site of HA gene showed similarity between poultry and wild birds, as well as to grp B-2.3.4.4 European-Asian H5N8 viruses. Since October 2020, new H5 reassortants with LPAI viruses from wild birds contributed the Neuraminidase (NA) glycoprotein, have appeared in Europe and created new H5 strains. A second global outbreak of a new H5 variant occurred in 2020-21 in Russia and the Palearctic region. Following this global outbreak, a second AIV-H5N8 outbreak appeared in Israel in 2020 during the autumn migration. The outbreak included meat and breeder turkeys, heavy breeders, broilers, game birds mainly black swans (Cygnus atratus), and wild birds. The 2021--22's AIV-H5N1 epidemic season was the largest so far in Europe and Eurasia, with about 2500 outbreaks in poultry and culling of 50 million birds, and about 3600 detections in wild birds. That outbreak followed the 2020's wave of the new AIV-H5N8. Following this epidemic, a third multi-focal outbreak of AIV-H5N1 occurred in Israel in 2021, in meat and breeder turkeys, heavy breeders, organic egg layers and meat ducks. The 2021's outbreak was characterized also by affecting many wild birds, not seen before in H5N1's outbreaks in Israel, while the largest affected population was Common cranes (Grus grus) on their migration routes from Russia and Scandinavia to Ethiopia and Sudan through Israel, undergoing mass mortality of almost 10,000 birds. Other threatened species like Marbled teal (Marmaronetta angustirostris) have died also due to this virus, as well as hundreds of Great white pelicans (Pelecanus onocrotalus), and several species of waterfowl and raptors. Classification of the viruses by whole genome sequencing (WGS) revealed the same group B-2.3.4.4 clade as in the H5N8 events and similarity between poultry and wild birds. This virus probably came from Russia in the autumn migration. A new outbreak of AIV-H5N1 began emerging in Israel from November 2022, in meat turkeys, heavy and light breeders, broilers. Unlike the 2021's outbreak, this virus affected only a few wild birds. HA gene sequencing revealed the virus belonged to the same group B-2.3.4.4 clade as in previous outbreaks. In conclusion, all avian influenza subtype H5 outbreaks in Israel followed the European-Eurasian outbreaks. The virus origin was from South East Asia, reaching Israel through spillover with migrating birds via Eurasia and Europe. [ABSTRACT FROM AUTHOR]