ArticleJournal of virology2010
The ESEV PDZ-binding motif of the avian influenza A virus NS1 protein protects infected cells from apoptosis by directly targeting Scribble.
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 67 papers.
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Who cites it
67 citing papers in PubMed, 97 citations in OpenAlex.
- Dissecting Cell Death Pathways in Influenza A Virus Infection: Comparative Insights from Human Models.Viruses · 2026Review
- The applications of live attenuated influenza a virus with modified NS1 gene.Molecular therapy. Nucleic acids · 2025Review
- 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
- Mechanistic Insights into Influenza A Virus-Induced Cell Death and Emerging Treatment Strategies.Veterinary sciences · 2024Review
- Structural Investigations of Interactions between the Influenza a Virus NS1 and Host Cellular Proteins.Viruses · 2023Review
- Viral subversion of the cell polarity regulator Scribble.Biochemical Society transactions · 2023Review
- Influenza Virus Infections in Polarized Cells.Viruses · 2022Review
- Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble.Viruses · 2022Article
- Could Interleukin-33 (IL-33) Govern the Outcome of an Equine Influenza Virus Infection? Learning from Other Species.Viruses · 2021Review
- 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
- Virus-associated disruption of mucosal epithelial tight junctions and its role in viral transmission and spread.Tissue barriers · 2021Review
- Review
- SARS-CoV-2 likely targets cellular PDZ proteins: a common tactic of pathogenic viruses.Future virology · 2021Article
- Divergent Mast Cell Responses Modulate Antiviral Immunity During Influenza Virus Infection.Frontiers in cellular and infection microbiology · 2021Review
- Molecular Evolution of the Influenza A Virus Non-structural Protein 1 in Interspecies Transmission and Adaptation.Frontiers in microbiology · 2021Review
- Viral PDZ Binding Motifs Influence Cell Behavior Through the Interaction with Cellular Proteins Containing PDZ Domains.Methods in molecular biology (Clifton, N.J.) · 2021Review
- The Scribble family in cancer: twentieth anniversary.Oncogene · 2020Review
- Roles of the Non-Structural Proteins of Influenza A Virus.Pathogens (Basel, Switzerland) · 2020Review
- Review
- The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection.International journal of molecular sciences · 2020Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The NS1 protein from influenza A viruses contains a four-amino-acid sequence at its carboxyl terminus that is termed the PDZ-binding motif (PBM). The NS1 PBM is predicted to bind to cellular PDZ proteins and functions as a virulence determinant in infected mice. ESEV is the consensus PBM sequence of avian influenza viruses, while RSKV is the consensus sequence of human viruses. Currently circulating highly pathogenic H5N1 influenza viruses encode an NS1 protein with the ESEV PBM. We identified cellular targets of the avian ESEV PBM and identified molecular mechanisms involved in its function. Using glutathione S-transferase (GST) pull-down assays, we found that the ESEV PBM enables NS1 to associate with the PDZ proteins Scribble, Dlg1, MAGI-1, MAGI-2, and MAGI-3. Because Scribble possesses a proapoptotic activity, we investigated the interaction between NS1 and Scribble. The association between NS1 and Scribble is direct and requires the ESEV PBM and two Scribble PDZ domains. We constructed recombinant H3N2 viruses that encode an H6N6 avian virus NS1 protein with either an ESEV or mutant ESEA PBM, allowing an analysis of the ESEV PBM in infections in mammalian cells. The ESEV PBM enhanced viral replication up to 4-fold. In infected cells, NS1 with the ESEV PBM relocalized Scribble into cytoplasmic puncta concentrated in perinuclear regions and also protected cells from apoptosis. In addition, the latter effect was eliminated by small interfering RNA (siRNA)-mediated Scribble depletion. This study shows that one function of the avian ESEV PBM is to reduce apoptosis during infection through disruption of Scribble's proapoptotic function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.