ArticleJournal of virology2010
Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- Epidemiological and Phylogenetic Analysis of Reassorted H10Nx Avian Influenza Viruses in Guangdong Province, China.Influenza and other respiratory viruses · 2026Article
- Cellular tropism of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses in human respiratory and bovine mammary epithelial cells.Microbiology spectrum · 2026Article
- Epidemiological and Genomic Characterization of H5 Subtype Avian Influenza Viruses in Jining City, 2024-2025.Pathogens (Basel, Switzerland) · 2026Article
- North American-origin influenza A (H10) viruses in Eurasian wild birds (2022-2024): implications for the emergence of human H10N5 virus.Emerging microbes & infections · 2025Article
- Article
- The C-terminal amino acid motifs of NS1 protein affect the replication and virulence of naturally NS-truncated H1N1 canine influenza virus.Emerging microbes & infections · 2024Article
- Phylogenetic and Molecular Characteristics of Wild Bird-Origin Avian Influenza Viruses Circulating in Poland in 2018-2022: Reassortment, Multiple Introductions, and Wild Bird-Poultry Epidemiological Links.Transboundary and emerging diseases · 2024Article
- Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes.International journal of molecular sciences · 2023Article
- Comparative Antigenicity and Pathogenicity of Two Distinct Genotypes of Highly Pathogenic Avian Influenza Viruses (H5N8) From Wild Birds in China, 2020-2021.Frontiers in microbiology · 2022Article
- 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.Emerging microbes & infections · 2021Article
- Article
- Preferential Selection and Contribution of Non-Structural Protein 1 (NS1) to the Efficient Transmission of Panzootic Avian Influenza H5N8 Virus Clades 2.3.4.4A and B in Chickens and Ducks.Journal of virology · 2021Article
- Airway tight junctions as targets of viral infections.Tissue barriers · 2021Article
- Molecular Evolution of the Influenza A Virus Non-structural Protein 1 in Interspecies Transmission and Adaptation.Frontiers in microbiology · 2021Review
- Influenza A Virus-Host Specificity: An Ongoing Cross-Talk Between Viral and Host Factors.Frontiers in microbiology · 2021Review
- Roles of the Non-Structural Proteins of Influenza A Virus.Pathogens (Basel, Switzerland) · 2020Review
- Inventory of molecular markers affecting biological characteristics of avian influenza A viruses.Virus genes · 2019Review
- Phylogeny, Pathogenicity, Transmission, and Host Immune Responses of Four H5N6 Avian Influenza Viruses in Chickens and Mice.Viruses · 2019Article
- Innate Immune Responses to Avian Influenza Viruses in Ducks and Chickens.Veterinary sciences · 2019Review
- IFN and cytokine responses in ducks to genetically similar H5N1 influenza A viruses of varying pathogenicity.The Journal of general virology · 2018Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We assessed the prediction that access of the viral NS1 protein to cellular PDZ domain protein networks enhances the virulence of highly pathogenic avian influenza A viruses. The NS1 proteins of most avian influenza viruses bear the C-terminal ligand sequence Glu-Ser-Glu-Val (ESEV) for PDZ domains present in multiple host proteins, whereas no such motif is found in the NS1 homologues of seasonal human virus strains. Previous analysis showed that a C-terminal ESEV motif increases viral virulence when introduced into the NS1 protein of mouse-adapted H1N1 influenza virus. To examine the role of the PDZ domain ligand motif in avian influenza virus virulence, we generated three recombinants, derived from the prototypic H5N1 influenza A/Vietnam/1203/04 virus, expressing NS1 proteins that either have the C-terminal ESEV motif or the human influenza virus RSKV consensus or bear a natural truncation of this motif, respectively. Cell biological analyses showed strong control of NS1 nuclear migration in infected mammalian and avian cells, with only minor differences between the three variants. The ESEV sequence attenuated viral replication on cultured human, murine, and duck cells but not on chicken fibroblasts. However, all three viruses caused highly lethal infections in mice and chickens, with little difference in viral titers in organs, mean lethal dose, or intravenous pathogenicity index. These findings demonstrate that a PDZ domain ligand sequence in NS1 contributes little to the virulence of H5N1 viruses in these hosts, and they indicate that this motif modulates viral replication in a strain- and host-dependent manner.
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