Abstract
Since 2014, highly pathogenic avian influenza (HPAI) H5N6 viruses have circulated in waterfowls and caused human infections in China, posing significant threats to the poultry industry and the public health. However, the genetics, pathogenicity and innate immune response of H5N6 HPAIVs in geese remain largely unknown. In this study, we analyzed the genetic characteristic of the two H5N6 viruses (GS38 and DK09) isolated from apparently healthy domestic goose and duck in live poultry markets (LPMs) of Southern China in 2016. Phylogenetic analysis showed that the HA genes of the two H5N6 viruses belonged to clade 2.3.4.4 and were clustered into the MIX-like group. The MIX-like group viruses have circulated in regions such as China, Japan, Korea, and Vietnam. The NA genes of the two H5N6 viruses were classified into the Eurasian sublineage. The internal genes including PB2, PB1, PA, NP, M, and NS of the two H5N6 viruses derived from the MIX-like. Therefore, our results suggested that the two H5N6 viruses were reassortants of the H5N1 and H6N6 viruses and likely derived from the same ancestor. Additionally, we evaluated the pathogenicity and transmission of the two H5N6 viruses in domestic geese. Results showed that both the two viruses caused serious clinical symptoms in all inoculated geese and led to high mortality in these birds. Both the two viruses were transmitted efficiently to contact geese and caused lethal infection in these birds. Furthermore, we found that mRNA of pattern recognition receptors (PRRs), interferons (IFNs), and stimulated genes (ISGs) exhibited different levels of activation in the lungs and spleens of the two H5N6 viruses-inoculated geese though did not protect these birds from H5N6 HPAIVs infection. Our results suggested that the clade 2.3.4.4 waterfowl-origin H5N6 HPAIVs isolated from LPMs of Southern China could cause high mortality in geese and innate immune-related genes were involved in the geese innate immune response to H5N6 HPAIVs infection. Therefore, we should pay more attention to the evolution, pathogenic variations of these viruses and enhance virological surveillance of clade 2.3.4.4 H5N6 HPAIVs in waterfowls in China.
Highlights
Avian influenza viruses belong to family Orthomyxoviridae, genus Influenza A virus
Recent epidemiological study demonstrated that H5N6 HPAIVs have replaced H5N1 HPAIVs as the dominant subtype in waterfowls in Southern China
From 2018 to Jan 2020, H5N6 HPAIVs have circulated in poultry and caused outbreaks in China, Vietnam, Japan, North Korea, and the Netherlands, etc., caused huge losses to the poultry industry
Summary
Avian influenza viruses belong to family Orthomyxoviridae, genus Influenza A virus. Based on the antigenicity difference of the two surface proteins Hemagglutinin (HA) and Neuraminidase (NA), influenza A virus can be divided into 18 HA (H1-H18) and 11 NA (N1-N11) [1,2]. Wild waterfowls are the reservoirs of the influenza A viruses and most of the HA and NA subtypes are identified in these birds. Among these subtypes, H5 and H7 subtype viruses occasionally acquired a multibasic cleavage site insert in their HA genes, which always led to the emergence of highly pathogenic avian influenza viruses. H5 and H7 subtype HPAIVs have widely circulated in China, posing great threat to poultry industries and public health [3,4,5]. There have been 861 cases of human infections with H5N1, which have posed great threat to public health [8]. Since 2014, there have been 24 cases of human infections with H5N6 viruses, posing a great threat to public health in China [8]. The pathogenicity and transmission of the H5N6 HPAIVs in geese remain largely unclear
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