ArticleProceedings of the National Academy of Sciences of the United States of America2012
Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Macrophage-Derived Factors with the Potential to Contribute to the Pathogenicity of HIV-1 and HIV-2: Roles of M-CSF and CXCL7.International journal of molecular sciences · 2025Article
- Review
- Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments.International journal of molecular sciences · 2022Review
- Categorizing Sequences of Concern by Function To Better Assess Mechanisms of Microbial Pathogenesis.Infection and immunity · 2022Review
- DNA immunotherapy targeting BARF1 induces potent anti-tumor responses against Epstein-Barr-virus-associated carcinomas.Molecular therapy oncolytics · 2022Article
- High-Risk Human Papillomavirus and Epstein-Barr Virus Coinfection: A Potential Role in Head and Neck Carcinogenesis.Biology · 2021Review
- Role of BamHI-A Rightward Frame 1 in Epstein-Barr Virus-Associated Epithelial Malignancies.Biology · 2020Review
- Review
- The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.PLoS pathogens · 2015Article
- Infectious Mononucleosis.Current topics in microbiology and immunology · 2015Review
- Epstein-Barr virus and nasopharyngeal carcinoma.Chinese journal of cancer · 2014Article
- CSF-1 receptor signaling in myeloid cells.Cold Spring Harbor perspectives in biology · 2014Review
- BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator.Reviews in medical virology · 2013Review
- Epstein-Barr virus-encoded BARF1 promotes proliferation of gastric carcinoma cells through regulation of NF-κB.Journal of virology · 2013Article
- An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.PLoS pathogens · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding of BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis.
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Registered trials
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.