ArticleJournal of biomedical science2021
Influenza a virus NS1 resembles a TRAF3-interacting motif to target the RNA sensing-TRAF3-type I IFN axis and impair antiviral innate immunity.
Article in Journal of biomedical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Dose-Dependent Alterations in Lung Immune Subpopulations in Influenza a Virus Infection.International journal of molecular sciences · 2026Article
- Suppression of Calcium Influx Reduces Coxsackievirus B3 Lethality With Elevated Interferon Beta Responses in Mice.Journal of medical virology · 2026Article
- Generation of an autophagy-targeting influenza A virus as live attenuated vaccine.Nature communications · 2026Article
- The Role of Viral Infection and Microbial Dysbiosis in Glaucoma: From Pathogenesis to Therapeutic Strategies.Viruses · 2026Review
- Emerging threats of H5N1 clade 2.3.4.4b: cross-species transmission, pathogenesis, and pandemic risk.Frontiers in cellular and infection microbiology · 2025Review
- Review
- Endosomes serve as signaling platforms for RIG-I ubiquitination and activation.Science advances · 2024Article
- Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.Pathogens (Basel, Switzerland) · 2024Review
- Exploring type I interferon pathway: virulent vs. attenuated strain of African swine fever virus revealing a novel function carried by MGF505-4R.Frontiers in immunology · 2024Article
- Virus versus host: influenza A virus circumvents the immune responses.Frontiers in microbiology · 2024Review
- The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.International journal of molecular sciences · 2023Article
- Upregulation of galectin-3 in influenza A virus infection promotes viral RNA synthesis through its association with viral PA protein.Journal of biomedical science · 2023Article
- The Roles of TRAF3 in Immune Responses.Disease markers · 2023Review
- Roles of RNA Sensors in Host Innate Response to Influenza Virus and Coronavirus Infections.International journal of molecular sciences · 2022Review
- Development of a Multi-Epitope Vaccine forInternational journal of molecular sciences · 2022Article
- The Roles of Ubiquitination in Pathogenesis of Influenza Virus Infection.International journal of molecular sciences · 2022Review
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12 authors at 2 institutions in 1 country.
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Abstract
backgroundInfluenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection. Yet, it remains unclear if IAV NS1 can exploit a common mechanism to counteract these RNA sensing pathways to type I IFN production at once, then promoting viral propagation in the host.
methodsLuciferase reporter assays were conducted to determine the effect of NS1 and its mutants on the RIG-I and TLR3 pathways to the activation of the IFN-β and NF-κB promoters. Coimmunoprecipitation and confocal microscopic analyses were used to the interaction and colocalization between NS1 and TRAF3. Ubiquitination assays were performed to study the effect of NS1 and its mutants on TRAF3 ubiquitination. A recombinant mutant virus carrying NS1 E152A/E153A mutations was generated by reverse genetics for biochemical, ex vivo, and in vivo analyses to explore the importance of NS1 E152/E153 residues in targeting the RNA sensing-TRAF3-type I IFN axis and IAV pathogenicity.
resultsHere we report that NS1 subverts the RIG-I, TLR3, and TLR7 pathways to type I IFN production through targeting TRAF3 E3 ubiquitin ligase. NS1 harbors a conserved FTEE motif (a.a. 150-153), in which the E152/E153 residues are critical for binding TRAF3 to block TRAF3 ubiquitination and type I IFN production by these RNA sensing pathways. A recombinant mutant virus carrying NS1 E152A/E153A mutations induces higher type I IFN production ex vivo and in vivo, and exhibits the attenuated phenotype in infected mice, indicating the importance of E152/E153 residues in IAV pathogenicity.
conclusionsTogether our work uncovers a novel mechanism of IAV NS1-mediated immune evasion to promote viral infection through targeting the RNA sensing-TRAF3-type I IFN axis.
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