The role of NS1 in H5N1 avian influenza viruses in unprecedented mass mortality events in gulls in 2021/2023

As reservoir hosts for avian influenza viruses (AIVs), wild waterfowl usually show no clinical signs of infection, while there is a constant circulation of low pathogenicity AIVs (LPAIVs) in the population. Since 2021, an increasing number of wild birds, including gulls (Laridae), have died after infection with HPAIV subtype H5N1 clade 2.3.4.4B. The genomic changes that led to the widespread and high virulence of this subtype in gulls remain to be elucidated.
We aimed to identify the effects of genetic markers that contribute to the high virulence of contemporary H5N1 clade 2.3.4.4B in gulls.
More than 40,000 sequences of AIV NS gene segments were analysed. The analysis revealed striking differences between the viruses originally circulating in gulls and the new H5N1 viruses. Interestingly, the NS gene segments of H5N1 appear to have completely replaced the segments of the original European gull-adapted viruses of the subtypes H13 and H16. Detailed analysis of the NS gene segment from both clusters has been undertaken to identify potential key mutations that could lead to the unexpected increase in virulence in gulls. Laboratory experiments have been conducted to evaluate the differences between the two H5N1 outbreak clusters and the H13/H16 gene segments on viral fitness and the host immune response.

Juliane Lang1, Elsayed M. Abdelwhab1 1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany

Notable outbreaks, field and molecular epidemiology, and surveillance in wild birds