Abstract
Since it firstly emerged in China in 2013, clade 2.3.4.4 H5N6 highly pathogenic avian influenza viruses (HPAIVs) has rapidly replaced predominant H5N1 to become the dominant H5 subtype in China, especially in ducks. Not only endemic in China, it also crossed the geographical barrier and emerged in South Korea, Japan, and Europe. Here, we analyzed the genetic properties of the clade 2.3.4.4 H5N6 HPAIVs with full genome sequences available online together with our own isolates. Phylogenetic analysis showed that clade 2.3.4.4 H5N6 HPAIVs continuously reassorted with local H5, H6, and H7N9/H9N2. Species analysis reveals that aquatic poultry and migratory birds became the dominant hosts of H5N6. Adaption to aquatic poultry might help clade 2.3.4.4 H5N6 better adapt to migratory birds, thus enabling it to become endemic in China. Besides, migratory birds might help clade 2.3.4.4 H5N6 transmit all over the world. Clade 2.3.4.4 H5N6 HPAIVs also showed a preference for α2,6-SA receptors when compared to other avian origin influenza viruses. Experiments in vitro and in vivo revealed that clade 2.3.4.4 H5N6 HPAIVs exhibited high replication efficiency in both avian and mammal cells, and it also showed high pathogenicity in both mice and chickens, demonstrating high risk to public health. Considering all the factors together, adaption to aquatic poultry and migratory birds helps clade 2.3.4.4 H5N6 overcome the geographical isolation, and it has potential to be the next influenza pandemic in the world, making it worthy of our attention.
Highlights
In 2013, clade 2.3.4.4 H5N6 highly pathogenic avian influenza viruses (HPAIVs) emerged in China for the first time [1,2]
We found that PB2 could be mainly classified into three lineages, which originated from China domestic clade
HPAIVs H5Nx such as H5N2, H5N8, and H5N6 have emerged and replaced predominant H5N1 and became the dominant subtypes
Summary
In 2013, clade 2.3.4.4 H5N6 HPAIVs emerged in China for the first time [1,2]. Surveillance of Chinese live poultry markets even showed that. H5N6 has become a dominant subtype in China, especially in aquatic poultry [8]. In China, H5N6 was found to transmit inter-species-wise between poultry and wild birds and to infect mammals such as swine, felines, and even humans [9,10]. Clade 2.3.4.4 H5N6 has become endemic in China and has the potential to be a world pandemic. Apart from H5N6, HPAIVs of clades 2.3.2, 2.3.4, and 7.2 of H5 have cocirculated predominantly in domestic poultry, especially in aquatic poultry in China, since 2007 [11,12,13]. Low pathogenic avian influenza viruses (LPAIVs), such as H9N2 and H6Nx, have circulated in the local poultry of
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