ArticleJournal of virology2014
Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 76 citations in OpenAlex.
- Poxvirus infection triggers remodeling of host m⁶A epitranscriptome and benefits from the m⁶A regulatory responses.Virology journal · 2026Article
- Review
- NSs: the multifaceted bunyavirus virulence factor.Npj viruses · 2025Review
- Review
- A Review of Nonhuman Primate Models of Rift Valley Fever Virus Infection: Progress, Challenge Strains, and Future Directions.Pathogens (Basel, Switzerland) · 2024Review
- RVFV virulence factor NSs triggers the mitochondrial MCL-1-BAK axis to activate pathogenic NLRP3 pyroptosis.PLoS pathogens · 2024Article
- Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.Viruses · 2024Article
- An LIR motif in the Rift Valley fever virus NSs protein is critical for the interaction with LC3 family members and inhibition of autophagy.PLoS pathogens · 2024Article
- Innate immune response against vector-borne bunyavirus infection and viral countermeasures.Frontiers in cellular and infection microbiology · 2024Review
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
- MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake.Viruses · 2023Article
- Mechanism of Immune Evasion in Mosquito-Borne Diseases.Pathogens (Basel, Switzerland) · 2023Review
- Mechanistic insight into the efficient packaging of antigenomic S RNA into Rift Valley fever virus particles.Frontiers in cellular and infection microbiology · 2023Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- An Overview of the Infectious Cycle of Bunyaviruses.Viruses · 2022Review
- The International Virus Bioinformatics Meeting 2022.Viruses · 2022Article
- Article
- Arm race between Rift Valley fever virus and host.Frontiers in immunology · 2022Review
- NSs of the mildly virulent sandfly fever Sicilian virus is unable to inhibit interferon signaling and upregulation of interferon-stimulated genes.The Journal of general virology · 2021Article
- Characterization of the Molecular Interactions That Govern the Packaging of Viral RNA Segments into Rift Valley Fever Phlebovirus Particles.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE: Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.
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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.