Dataset Information

Risk Assessment for Highly Pathogenic Avian Influenza A(H5N6/H5N8) Clade 2.3.4.4 Viruses.

ABSTRACT: The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.

SUBMITTER: Bui CHT

PROVIDER: S-EPMC8462306 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

Dataset Information

Risk Assessment for Highly Pathogenic Avian Influenza A(H5N6/H5N8) Clade 2.3.4.4 Viruses.

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