ArticleEmerging microbes & infections2021
The C-terminus of non-structural protein 1 (NS1) in H5N8 clade 2.3.4.4 avian influenza virus affects virus fitness in human cells and virulence in mice.
Article in Emerging microbes & infections, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Decoding the lung-brain axis in influenza: from pulmonary infection to central nervous system injury.Journal of neuroinflammation · 2026Review
- On the brink of emergence: an evolutionary approach to Influenza A virus H5N1 isolated from humans.Virus research · 2026Article
- Host-specific functional evolution of seal influenza A virus NS1 protein following avian-to-seal transmission.Journal of virology · 2026Article
- Avian influenza overview December 2025-February 2026.EFSA journal. European Food Safety Authority · 2026Article
- Rapid surge of reassortant A(H1N1) influenza viruses in Danish swine and their zoonotic potential.Emerging microbes & infections · 2025Article
- Avian influenza overview September-November 2025.EFSA journal. European Food Safety Authority · 2025Article
- A Rapid Review Contrasting the Evidence on Avian Influenza A(H5Nx) Clades 2.3.4.4b and 2.3.2.1c in Humans.Zoonoses and public health · 2025Review
- H5N1 2.3.4.4b: a review of mammalian adaptations and risk of pandemic emergence.The Journal of general virology · 2025Review
- Influenza Virus Genomic Mutations, Host Barrier and Cross-species Transmission.Current genomics · 2025Review
- Article
- Review
- Dual receptor-binding, infectivity, and transmissibility of an emerging H2N2 low pathogenicity avian influenza virus.Nature communications · 2024Article
- Evolution and international transmission of H3N2 canine influenza A viruses from Korea during 2014-2017.Journal of veterinary science · 2023Article
- Multiple infections with H5N8 subtype high pathogenicity avian influenza viruses in a feral mallard.The Journal of veterinary medical science · 2023Article
- Highly pathogenic avian influenza (A/H5N1) virus outbreaks in Lesotho, May 2021.Emerging microbes & infections · 2022Article
- Evolutionary and Mutational Characterization of the First H5N8 Subtype Influenza A Virus in Humans.Pathogens (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Avian influenza viruses (AIV) H5N8 clade 2.3.4.4 pose a public health threat but the viral factors relevant for its potential adaptation to mammals are largely unknown. The non-structural protein 1 (NS1) of influenza viruses is an essential interferon antagonist. It commonly consists of 230 amino acids, but variations in the disordered C-terminus resulted in truncation or extension of NS1 with a possible impact on virus fitness in mammals. Here, we analysed NS1 sequences from 1902 to 2020 representing human influenza viruses (hIAV) as well as AIV in birds, humans and other mammals and with an emphasis on the panzootic AIV subtype H5N8 clade 2.3.4.4A (H5N8-A) from 2013 to 2015 and clade 2.3.4.4B (H5N8-B) since 2016. We found a high degree of prevalence for short NS1 sequences among hIAV, zoonotic AIV and H5N8-B, while AIV and H5N8-A had longer NS1 sequences. We assessed the fitness of recombinant H5N8-A and H5N8-B viruses carrying NS1 proteins with different lengths in human cells and in mice. H5N8-B with a short NS1, similar to hIAV or AIV from a human or other mammal-origins, was more efficient at blocking apoptosis and interferon-induction without a significant impact on virus replication in human cells. In mice, shortening of the NS1 of H5N8-A increased virus virulence, while the extension of NS1 of H5N8-B reduced virus virulence and replication. Taken together, we have described the biological impact of variation in the NS1 C-terminus in hIAV and AIV and shown that this affects virus fitness
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