Characterization of highly pathogenic avian influenza H5Nx viruses in the ferret model

Joanna A Pulit-Penaloza,Xiangjie Sun,Claudia Pappas,Hui Zeng,Terrence M Tumpey,Nicole Brock,Jessica A Belser,Taronna R Maines

doi:10.1038/s41598-020-69535-5

Abstract

Highly pathogenic avian influenza (HPAI) H5 viruses, of the A/goose/Guangdong/1/1996 lineage, have exhibited substantial geographic spread worldwide since the first detection of H5N1 virus in 1996. Accumulation of mutations in the HA gene has resulted in several phylogenetic clades, while reassortment with other avian influenza viruses has led to the emergence of new virus subtypes (H5Nx), notably H5N2, H5N6, and H5N8. H5Nx viruses represent a threat to both the poultry industry and human health and can cause lethal human disease following virus exposure. Here, HPAI H5N6 and H5N2 viruses (isolated between 2014 and 2017) of the 2.3.4.4 clade were assessed for their capacity to replicate in human respiratory tract cells, and to cause disease and transmit in the ferret model. All H5N6 viruses possessed increased virulence in ferrets compared to the H5N2 virus; however, pathogenicity profiles varied among the H5N6 viruses tested, from mild infection with sporadic virus dissemination beyond the respiratory tract, to severe disease with fatal outcome. Limited transmission between co-housed ferrets was observed with the H5N6 viruses but not with the H5N2 virus. In vitro evaluation of H5Nx virus replication in Calu-3 cells and the identification of mammalian adaptation markers in key genes associated with pathogenesis supports these findings.

Highlights

Pathogenic avian influenza (HPAI) H5 viruses, of the A/goose/Guangdong/1/1996 lineage, have exhibited substantial geographic spread worldwide since the first detection of H5N1 virus in 1996
As each human infection with a zoonotic strain provides an opportunity for virus adaptation to a new species, it is important to monitor the acquisition of human adaptation markers in newly emerging avian influenza strains, especially those associated with human infection
The first Highly pathogenic avian influenza (HPAI) H5N6 human infection was reported in China in April 2014 and since 24 human cases were reported, some of which were fatal[6]

Summary

Introduction

Pathogenic avian influenza (HPAI) H5 viruses, of the A/goose/Guangdong/1/1996 lineage, have exhibited substantial geographic spread worldwide since the first detection of H5N1 virus in 1996. Accumulation of mutations in the HA gene has resulted in several phylogenetic clades, while reassortment with other avian influenza viruses has led to the emergence of new virus subtypes (H5Nx), notably H5N2, H5N6, and H5N8. HPAI H5N6 and H5N2 viruses (isolated between 2014 and 2017) of the 2.3.4.4 clade were assessed for their capacity to replicate in human respiratory tract cells, and to cause disease and transmit in the ferret model. A total of 24 laboratory-confirmed human cases have been reported in China that include at least 7 deaths[6] Considering their rapid evolution, prevalence, and capacity to cause human infection with a high mortality rate, clade 2.3.4.4 HPAI H5Nx viruses pose a serious risk to both the poultry industry and human health[12]. Molecular markers related to human adaptation have been reported in the polymerase genes of some HPAI H5N6 human isolates, suggesting enhanced polymerase activity in mammalian cells[18]

Methods

Results

Conclusion