ArticleThe EMBO journal2019
Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- RNA helicase DDX3X promotes NK cell survival by supporting MCL1 expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Review
- Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.International journal of molecular sciences · 2024Review
- Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Pathogenicity and virulence of influenza.Virulence · 2023Review
- Review
- The Roles of Ubiquitination in Pathogenesis of Influenza Virus Infection.International journal of molecular sciences · 2022Review
- Pleiotropic Effects of Influenza H1, H3, and B Baloxavir-Resistant Substitutions on Replication, Sensitivity to Baloxavir, and Interferon Expression.Antimicrobial agents and chemotherapy · 2022Article
- RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling.Microorganisms · 2021Review
- Immunity to Influenza Infection in Humans.Cold Spring Harbor perspectives in medicine · 2021Review
- The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.PLoS pathogens · 2021Article
- DDX3X Links NLRP11 to the Regulation of Type I Interferon Responses and NLRP3 Inflammasome Activation.Frontiers in immunology · 2021Article
- Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication.PLoS pathogens · 2020Article
- Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus.PLoS pathogens · 2020Article
- Review
- DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs.Molecules (Basel, Switzerland) · 2020Review
- Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins.Journal of biosciences · 2020Review
- Stabilization of Intrinsically Disordered DKK2 Protein by Fusion to RNA-Binding Domain.International journal of molecular sciences · 2019Article
- Human infection with a novel reassortant Eurasian-avian lineage swine H1N1 virus in northern China.Emerging microbes & infections · 2019Article
- Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.
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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.