ArticleJournal of virology2021
Phosphorylation of Influenza A Virus NS1 at Serine 205 Mediates Its Viral Polymerase-Enhancing Function.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Host-specific functional evolution of seal influenza A virus NS1 protein following avian-to-seal transmission.Journal of virology · 2026Article
- Post-translational modification networks as master regulators of influenza virus replication, host adaptation, and immune evasion.Frontiers in immunology · 2026Review
- The roles of post-translational modifications in the pathogenesis of RNA viruses: allies or adversaries?Frontiers in microbiology · 2026Review
- Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice.Emerging microbes & infections · 2025Article
- Article
- Pyruvate kinase M2 modulates Japanese encephalitis virus replication in neuronal cells.The Journal of general virology · 2025Article
- Nonstructural Protein 1 of Influenza A (NS1A) Demonstrates Strain-Specific dsRNA Binding Capabilities.ACS infectious diseases · 2025Article
- Overview of host-directed antiviral targets for future research and drug development.Acta pharmaceutica Sinica. B · 2025Review
- The applications of live attenuated influenza a virus with modified NS1 gene.Molecular therapy. Nucleic acids · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Phosphorylation of S-S-S Motif in Nuclear Export Protein (NEP) Plays a Critical Role in Viral Ribonucleoprotein (vRNP) Nuclear Export of Influenza A and B Viruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission.mBio · 2024Review
- Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice.Virologica Sinica · 2024Article
- Unveiling the role of host kinases at different steps of influenza A virus life cycle.Journal of virology · 2024Review
- Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1.Frontiers in cellular and infection microbiology · 2024Review
- PRMT5 Facilitates Infectious Bursal Disease Virus Replication through Arginine Methylation of VP1.Journal of virology · 2023Article
- Phosphorylation of VP1 Mediated by CDK1-Cyclin B1 Facilitates Infectious Bursal Disease Virus Replication.Journal of virology · 2023Article
- Interactome Profiling of N-Terminus-Truncated NS1 Protein of Influenza A Virus Reveals Role of 14-3-3γ in Virus Replication.Pathogens (Basel, Switzerland) · 2022Article
- Influenza A Virus Uses PSMA2 for Downregulation of the NRF2-Mediated Oxidative Stress Response.Journal of virology · 2022Article
- NS1: A Key Protein in the "Game" Between Influenza A Virus and Host in Innate Immunity.Frontiers in cellular and infection microbiology · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza A virus (IAV) nonstructural protein 1 (NS1) is a protein with multiple functions that are regulated by phosphorylation. Phosphoproteomic screening of H1N1 virus-infected cells revealed that NS1 was phosphorylated at serine 205 in intermediate stages of the viral life cycle. Interestingly, S205 is one of six amino acid changes in NS1 of post-pandemic H1N1 viruses currently circulating in humans compared to the original swine-origin 2009 pandemic (H1N1pdm09) virus, suggesting a role in host adaptation. To identify NS1 functions regulated by S205 phosphorylation, we generated recombinant PR8 H1N1 NS1 mutants with S205G (nonphosphorylatable) or S205N (H1N1pdm09 signature), as well as H1N1pdm09 viruses harboring the reverse mutation NS1 N205S or N205D (phosphomimetic). Replication of PR8 NS1 mutants was attenuated relative to wild-type (WT) virus replication in a porcine cell line. However, PR8 NS1 S205N showed remarkably higher attenuation than PR8 NS1 S205G in a human cell line, highlighting a potential host-independent advantage of phosphorylatable S205, while an asparagine at this position led to a potential host-specific attenuation. Interestingly, PR8 NS1 S205G did not show polymerase activity-enhancing functions, in contrast to the WT, which can be attributed to diminished interaction with cellular restriction factor DDX21. Analysis of the respective kinase mediating S205 phosphorylation indicated an involvement of casein kinase 2 (CK2). CK2 inhibition significantly reduced the replication of WT viruses and decreased NS1-DDX21 interaction, as observed for NS1 S205G. In summary, NS1 S205 is required for efficient NS1-DDX21 binding, resulting in enhanced viral polymerase activity, which is likely to be regulated by transient phosphorylation.
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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.