Genetic Determinants for Virulence and Transmission of the Panzootic Avian Influenza Virus H5N8 Clade 2.3.4.4 in Pekin Ducks

Abstract

Since 2014, several waves of avian influenza virus (AIV) H5N8 of clade 2.3.4.4 occurred globally on unprecedented levels. Unlike viruses in the first wave in 2014–2015 (H5N8-A), viruses in 2015–2016 (H5N8-B) exhibited unusually high pathogenicity (HP) in wild and domestic ducks.

Conserved Expression and Functionality of Furin between Chickens and Ducks as an Activating Protease of Highly Pathogenic Avian Influenza Virus Hemagglutinins

“…The replication of HPAIVs in the endothelium is a hallmark of HPAIV infections in terrestrial poultry and most likely contributes to HPAIV systemic dissemination, pathogenesis, and high mortality ( 63 – 65 ). In ducks, endothelial cells are not positive for viral antigen, with the exception of ducks infected with H5N8 HPAIVs from 2016 ( 16 , 22 , 23 ), and endotheliotropism-associated clinical manifestations such as hemorrhage and edema are not observed ( 13 , 15 , 21 , 36 ). Here, we concurrently observed the trypsin-independent replication of HPAIV, as was shown by us before ( 25 ), and expression of PC mRNA in duck endothelial cells.…”

“…In contrast, HPAIV HAs are cleaved by ubiquitous furin-like proteases, which allow for virus replication in a plethora of different tissues and consequently systemic virus dissemination in gallinaceous poultry ( 35 ). In contrast, the presence of an MBCS does not necessarily lead to widespread replication of AIVs in wild birds ( 36 ), except for some HPAIVs from the Gs/Gd lineage ( 13 , 16 , 22 ). Therefore, the difference in HPAIV tropism between poultry and wild aquatic birds might also be related to a certain extent to expression and activity differences of furin-like proteases.…”

“…Their disease severity depends on the bird species, viral strain, age, and infection history ( 12 , 13 , 17 – 21 ). Still, the disease manifestations presented by Gs/Gd HPAIV-infected wild aquatic birds are distinct from those in poultry, as endotheliotropism and hemorrhage are seldom observed ( 14 , 16 , 22 , 23 ). The reasons behind this stark difference in HPAIV pathogenesis between gallinaceous poultry and wild aquatic birds have not been fully elucidated, but differences in the induction of antiviral and inflammatory responses are thought to be important ( 24 – 28 ).…”

The episodic resurgence of highly pathogenic avian influenza H5 virus

“…Experimental animal infections showed clade 2.3.4.4 viruses were associated with increased adaptation and reduced virulence in wild ducks compared to earlier H5N1 lineages (20-23). Repeated outbreaks in wild birds from 2016 were due to clade 2.3.4.4.b H5N8 viruses that originated in China (16) and had a relative increase in virulence in ducks (24, 25). Furthermore, a reassortant HPAI H5N1 subtype which evolved from clade 2.3.4.4b viruses, has almost entirely replaced clade 2.3.4.4.b H5N8 viruses ( Fig.…”

“…Repeated outbreaks in wild birds from 2016 were due to clade 2.3.4.4.b H5N8 viruses that originated in China (16) and had a relative increase in virulence in ducks (24,25). Furthermore, a reassortant HPAI H5N1 subtype which evolved from clade 2.3.4.4b viruses, has almost entirely replaced clade 2.3.4.4.b H5N8 viruses (Fig.…”