ArticleJournal of virology2013
Synergistic effect of the PDZ and p85β-binding domains of the NS1 protein on virulence of an avian H5N1 influenza A virus.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Rule-based meta-analysis reveals the major role of PB2 in influencing influenza A virus virulence in mice.BMC genomics · 2019Pooled it
- Article
- Screening for influenza B virus NS1-interacting host proteins and characterization of interactions with hnRNPA0 and DDX39B.Virus genes · 2026Article
- Genomic surveillance of influenza A virus in live bird markets during the COVID-19 pandemic.Veterinary world · 2025Article
- HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.Emerging microbes & infections · 2024Article
- Vaccination and Antiviral Treatment against Avian Influenza H5Nx Viruses: A Harbinger of Virus Control or Evolution.Vaccines · 2023Review
- 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
- Unveiling New Druggable Pockets in Influenza Non-Structural Protein 1: NS1-Host Interactions as Antiviral Targets for Flu.International journal of molecular sciences · 2023Article
- Structural insight into the Scribble PDZ domains interaction with the oncogenic Human T-cell lymphotrophic virus-1 (HTLV-1) Tax1 PBM.The FEBS journal · 2023Article
- Molecular basis of Tick Born encephalitis virus NS5 mediated subversion of apico-basal cell polarity signalling.The Biochemical journal · 2022Article
- Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble.Viruses · 2022Article
- 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
- Molecular Characterization of Closely Related H6N2 Avian Influenza Viruses Isolated from Turkey, Egypt, and Uganda.Viruses · 2021Article
- The Two Sides of the Same Coin-Influenza Virus and Intracellular Signal Transduction.Cold Spring Harbor perspectives in medicine · 2021Review
- Roles of the Non-Structural Proteins of Influenza A Virus.Pathogens (Basel, Switzerland) · 2020Review
- Upsetting the Balance: When Viruses Manipulate Cell Polarity Control.Journal of molecular biology · 2018Review
- Review
- Diversity of Influenza A(H5N1) Viruses in Infected Humans, Northern Vietnam, 2004-2010.Emerging infectious diseases · 2018Article
- Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.Journal of virology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
The influenza A virus NS1 protein affects virulence through several mechanisms, including the host's innate immune response and various signaling pathways. Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype continue to evolve through reassortment and mutations. Our recent phylogenetic analysis identified a group of HPAI H5N1 viruses with two characteristic mutations in NS1: the avian virus-type PDZ domain-binding motif ESEV (which affects virulence) was replaced with ESKV, and NS1-138F (which is highly conserved among all influenza A viruses and may affect the activation of the phosphatidylinositol 3-kinase [PI3K]/Akt signaling pathway) was replaced with NS1-138Y. Here, we show that an HPAI H5N1 virus (A/duck/Hunan/69/2004) encoding NS1-ESKV and NS1-138Y was confined to the respiratory tract of infected mice, whereas a mutant encoding NS1-ESEV and NS1-138F caused systemic infection and killed mice more efficiently. Mutation of either one of these sites had small effects on virulence. In addition, we found that the amino acid at NS1-138 affected not only the induction of the PI3K/Akt pathway but also the interaction of NS1 with cellular PDZ domain proteins. Similarly, the mutation in the PDZ domain-binding motif of NS1 altered its binding to cellular PDZ domain proteins and affected Akt phosphorylation. These findings suggest a functional interplay between the mutations at NS1-138 and NS1-229 that results in a synergistic effect on influenza virulence.
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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.