Variable impact of the hemagglutinin polybasic cleavage site on virulence and pathogenesis of avian influenza H7N7 virus in chickens, turkeys and ducks

David Scheibner,Olanrewaju I. Fatola,Reiner Ulrich,Thomas C. Mettenleiter,Jutta Veits,Timm C. Harder,Ahmed H. Salaheldin,Annika Graaf,Elsayed M. Abdelwhab,Marcel Gischke

doi:10.1038/s41598-019-47938-3

David Scheibner, Olanrewaju I. Fatola + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-47938-3

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Journal: Scientific Reports	Publication Date: Aug 9, 2019
Citations: 25	License type: open-access

Affiliation: Friedrich-Loeffler-Institut

Abstract

Avian influenza viruses (AIV) are classified into 16 hemagglutinin (HA; H1-H16) and 9 neuraminidase (NA; N1-N9) subtypes. All AIV are low pathogenic (LP) in birds, but subtypes H5 and H7 AIV can evolve into highly pathogenic (HP) forms. In the last two decades evolution of HPAIV H7 from LPAIV has been frequently reported. However, little is known about the pathogenesis and evolution of HP H7 from LP ancestors particularly, in non-chicken hosts. In 2015, both LP and HP H7N7 AIV were isolated from chickens in two neighbouring farms in Germany. Here, the virulence of these isogenic H7N7 LP, HP and LP virus carrying a polybasic HA cleavage site (HACS) from HP (designated LP-Poly) was studied in chickens, turkeys and different duck breeds. The LP precursor was avirulent in all birds. In contrast, all inoculated and contact chickens and turkeys died after infection with HP. HP infected Pekin and Mallard ducks remained clinically healthy, while Muscovy ducks exhibited moderate depression and excreted viruses at significantly higher amounts. The polybasic HACS increased virulence in a species-specific manner with intravenous pathogenicity indices of 3.0, 1.9 and 0.2 in chickens, turkeys and Muscovy ducks, respectively. Infection of endothelial cells was only observed in chickens. In summary, Pekin and Mallard were more resistant to HPAIV H7N7 than chickens, turkeys and Muscovy ducks. The polybasic HACS was the main determinant for virulence and endotheliotropism of HPAIV H7N7 in chickens, whereas other viral and/or host factors play an essential role in virulence and pathogenesis in turkeys and ducks.

Highlights

Avian influenza A viruses (AIV) are members of the family Orthomyxoviridae
No significant differences were observed in chicken embryo kidney (CEK) cells (Fig. 1 panel b)
In Madin-Darby canine kidney cells type II (MDCKII), low pathogenic (LP)-Poly replicated to higher titres than the LP and highly pathogenic (HP) viruses (Fig. 1 panel b), which, was not statistically significant (P > 0.05)

Summary

Introduction

Avian influenza A viruses (AIV) are members of the family Orthomyxoviridae. They are differentiated according to the antigenicity of the hemagglutinin (HA) and neuraminidase (NA) proteins into 16 HA (H1 to H16) and 9 NA (N1 to N9) subtypes[1]. HA is a surface glycoprotein which mediates virus attachment and fusion with the host cell endosomal membrane It plays essential roles in virulence, immunogenicity and interspecies transmission (e.g. from birds to mammals)[2]. Only H5 and H7 subtypes can evolve from LP precursors to HPAIV by acquisition of mutations in CS of the HA protein[4] These mutations are unique to each HPAIV and can modulate virulence and bird-to-bird transmission[8,9,10,11,12]. The impact of the polybasic HACS on virus replication, virulence, bird-to-bird transmission and tropism was investigated in chickens, turkeys and different duck breeds

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