ArticlePLoS pathogens2017
A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling.
Article in PLoS pathogens, 2017. 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, 30 citations in OpenAlex.
- Host-Orf virus interactions: A comprehensive review of pathogenesis and immune evasion mechanisms.Virulence · 2026Review
- Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation.PLoS pathogens · 2026Article
- Development and application of a novel indirect ELISA based on recombinant ORFV114 protein for serodiagnosis of Orf virus in goats.Veterinary research communications · 2025Article
- Advancing ORFV-Based Therapeutics to the Clinical Stage.Reviews in medical virology · 2025Review
- Temporal and spatial characterization of keratinocytes supporting orf virus replication.Frontiers in cellular and infection microbiology · 2024Article
- Bovine papular stomatitis virus as a vaccine vector for cattle.The Journal of general virology · 2023Article
- 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
- The cooperation between orf virus andFrontiers in cellular and infection microbiology · 2023Review
- Establishment of a sheep immortalization cell line for generating and amplifying Orf virus recombinants.Frontiers in veterinary science · 2022Article
- The novel ORFV protein ORFV113 activates LPA-p38 signaling.PLoS pathogens · 2021Article
- Orf Virus ORF120 Protein Positively Regulates the NF-κB Pathway by Interacting with G3BP1.Journal of virology · 2021Article
- pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production.PLoS pathogens · 2021Article
- Molecular Insights into the Genetic Variability of ORF Virus in a Mediterranean Region (Sardinia, Italy).Life (Basel, Switzerland) · 2021Article
- Porcine epidemic diarrhea virus nsp14 inhibits NF-κB pathway activation by targeting the IKK complex and p65.Animal diseases · 2021Article
- NF-κB as an Important Factor in Optimizing Poxvirus-Based Vaccines against Viral Infections.Pathogens (Basel, Switzerland) · 2020Review
- Curcumin suppressed proliferation and migration of human retinoblastoma cells through modulating NF-κB pathway.International ophthalmology · 2020Article
- Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50.Frontiers in immunology · 2020Article
- Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017.Emerging infectious diseases · 2019Article
- Immune Ecosystem of Virus-Infected Host Tissues.International journal of molecular sciences · 2018Review
- Orf Virus Encoded Protein ORFV119 Induces Cell Apoptosis Through the Extrinsic and Intrinsic Pathways.Frontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent. ORFV119 was shown to inhibit IKK complex activation early in infection. Consistent with IKK inhibition, ORFV119 also interacted with TNF receptor associated factor 2 (TRAF2), an adaptor protein recruited to signaling complexes upstream of IKK in infected cells. ORFV119-TRAF2 interaction was enhanced in the presence of pRb, suggesting that ORFV119-pRb complex is required for efficient interaction with TRAF2. Additionally, transient expression of ORFV119 in uninfected cells was sufficient to inhibit TNFα-induced IKK activation and NF-κB signaling, indicating that no other viral proteins are required for the effect. Infection of sheep with ORFV lacking the ORFV119 gene led to attenuated disease phenotype, indicating that ORFV119 contributes to virulence in the natural host. ORFV119 represents the first poxviral protein to interfere with NF-κB signaling through interaction with pRb.
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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.