Abstract Title
Selective Disadvantages of Neuraminidase Stalk Deletion in Non-H5N1 Avian Influenza Viruses in Chickens, Turkeys or Ducks
Abstract
The adaptation of avian influenza viruses (AIVs) from wild to terrestrial birds is often linked to a deletion in the stalk domain of the viral glycoprotein neuraminidase (NA). While studies have largely focused on H5N1 viruses—where the N1-stalk deletion increases virulence, replication, and transmission in chickens—less is understood about the effects of NA stalk deletions (NAdel) in other subtypes, particularly in turkeys and ducks.
In this study, we used reverse genetics to create recombinant H5N1, H5N3, H7N7, and H5N8 AIVs with either a long (NA-long) or short (NA-short) stalk. We evaluated virus fitness in experimentally inoculated chickens, ducks, and turkeys, as well as transmission to co-housed birds. Additionally, we assessed virus replication in various cell cultures and examined NA activity using both cell-free and cell-based assays.
Our findings showed that the NA stalk domain influences virus fitness in a strain- and species-specific manner. In chickens, the H5N1 NA-long variant exhibited significantly lower virulence and transmission, whereas H5N3, H7N7, and H5N8 (clade 2.3.4.4B) showed no notable changes in virulence with NA-stalk variations. Interestingly, NA-short variants reduced replication and transmission in H5N3, H7N7, and H5N8 AIVs, and similarly decreased replication and spread in H5N8-infected ducks. In vitro, NA stalk length modulated NA activity and replication efficiency across strains.
Overall, our data suggest that NAdel, per se, provide a selective disadvantage for non-H5N1 viruses in chickens, turkeys, and ducks, which may explain the limited occurrence of NA stalk deletions in non-H5N1 strains, especially in wild bird populations.
In this study, we used reverse genetics to create recombinant H5N1, H5N3, H7N7, and H5N8 AIVs with either a long (NA-long) or short (NA-short) stalk. We evaluated virus fitness in experimentally inoculated chickens, ducks, and turkeys, as well as transmission to co-housed birds. Additionally, we assessed virus replication in various cell cultures and examined NA activity using both cell-free and cell-based assays.
Our findings showed that the NA stalk domain influences virus fitness in a strain- and species-specific manner. In chickens, the H5N1 NA-long variant exhibited significantly lower virulence and transmission, whereas H5N3, H7N7, and H5N8 (clade 2.3.4.4B) showed no notable changes in virulence with NA-stalk variations. Interestingly, NA-short variants reduced replication and transmission in H5N3, H7N7, and H5N8 AIVs, and similarly decreased replication and spread in H5N8-infected ducks. In vitro, NA stalk length modulated NA activity and replication efficiency across strains.
Overall, our data suggest that NAdel, per se, provide a selective disadvantage for non-H5N1 viruses in chickens, turkeys, and ducks, which may explain the limited occurrence of NA stalk deletions in non-H5N1 strains, especially in wild bird populations.
Co-Author(s)
David Scheibner1, Maryna Kuryshko1, Thomas C. Mettenleiter2, and Elsayed M. Abdelwhab1
1Friedrich Loeffler Institute, Institute of Molecular Virology and Cell Biology (IMVZ), Greifswald - Insel Riems, Germany
2Friedrich Loeffler Institute, Greifswald - Insel Riems, Germany
Abstract Category
Transmission pathways, pathobiology, immune responses