ArticleProceedings of the National Academy of Sciences of the United States of America2019
NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKKEmerging microbes & infections · 2024Article
- The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.Emerging microbes & infections · 2024Article
- GM-CSF and IL-21-armed oncolytic vaccinia virus significantly enhances anti-tumor activity and synergizes with anti-PD1 immunotherapy in pancreatic cancer.Frontiers in immunology · 2024Article
- Article
- The MGF300-2R protein of African swine fever virus is associated with viral pathogenicity by promoting the autophagic degradation of IKKα and IKKβ through the recruitment of TOLLIP.PLoS pathogens · 2023Article
- Radiation-Induced Cellular Senescence Reduces Susceptibility of Glioblastoma Cells to Oncolytic Vaccinia Virus.Cancers · 2023Article
- Oncolytic vaccinia virus and cancer immunotherapy.Frontiers in immunology · 2023Review
- Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation.The Journal of general virology · 2022Article
- How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses.Pathogens (Basel, Switzerland) · 2022Review
- Viral-mediated activation and inhibition of programmed cell death.PLoS pathogens · 2022Review
- Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65.Viruses · 2022Article
- Small Hero with Great Powers: Vaccinia Virus E3 Protein and Evasion of the Type I IFN Response.Biomedicines · 2022Review
- Molecular mimicry of NF-κB by vaccinia virus protein enables selective inhibition of antiviral responses.Nature microbiology · 2022Article
- IRAK1-dependent Regnase-1-14-3-3 complex formation controls Regnase-1-mediated mRNA decay.eLife · 2021Article
- Poxvirus Interactions with the Host Ubiquitin System.Pathogens (Basel, Switzerland) · 2021Review
- African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation.Viruses · 2021Article
- Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.PLoS pathogens · 2021Article
- Progress on Poxvirus E3 Ubiquitin Ligases and Adaptor Proteins.Frontiers in immunology · 2021Review
- Poxviral Strategies to Overcome Host Cell Apoptosis.Pathogens (Basel, Switzerland) · 2020Review
- Leaky scanning translation generates a second A49 protein that contributes to vaccinia virus virulence.The Journal of general virology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vaccinia virus protein A49 inhibits NF-κB activation by molecular mimicry and has a motif near the N terminus that is conserved in IκBα, β-catenin, HIV Vpu, and some other proteins. This motif contains two serines, and for IκBα and β-catenin, phosphorylation of these serines enables recognition by the E3 ubiquitin ligase β-TrCP. Binding of IκBα and β-catenin by β-TrCP causes their ubiquitylation and thereafter proteasome-mediated degradation. In contrast, HIV Vpu and VACV A49 are not degraded. This paper shows that A49 is phosphorylated at serine 7 but not serine 12 and that this is necessary and sufficient for binding β-TrCP and antagonism of NF-κB. Phosphorylation of A49 S7 occurs when NF-κB signaling is activated by addition of IL-1β or overexpression of TRAF6 or IKKβ, the kinase needed for IκBα phosphorylation. Thus, A49 shows beautiful biological regulation, for it becomes an NF-κB antagonist upon activation of NF-κB signaling. The virulence of viruses expressing mutant A49 proteins or lacking A49 (vΔA49) was tested. vΔA49 was attenuated compared with WT, but viruses expressing A49 that cannot bind β-TrCP or bind β-TrCP constitutively had intermediate virulence. So A49 promotes virulence by inhibiting NF-κB activation and by another mechanism independent of S7 phosphorylation and NF-κB antagonism. Last, a virus lacking A49 was more immunogenic than the WT virus.
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