Structure of the Epstein-Barr Virus Oncogene BARF1

Tarbouriech, Nicolas; Ruggiero, Florence; Turenne-Tessier, Mireille de; Ooka, Tadamasa; Burmeister, W.P.

doi:10.1016/j.jmb.2006.03.056

Cited by 43 publications

(65 citation statements)

References 49 publications

(38 reference statements)

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“…The BARF1 hexamer in the complex is similar to the free BARF1 structure [Protein Data Bank (PDB) ID code 2CH8], in which each BARF1 protomer contains two Ig-like domains (Ig1 and Ig2) joined together tightly with a hydrophobic boundary (18). The ring is formed by the N-terminal Ig1 docking face-toface on the Ig1 of a neighboring BARF1 protomer and the C-terminal Ig2 docking side-to-side on the Ig2 of another neighboring BARF1 protomer.…”

Section: Resultsmentioning

confidence: 99%

“…A main-chain hydrogen bond (BARF1 Val38 N-M-CSF Asp63 O) also is formed because of this conformational change, which pulls the end of the M-CSF αB helix toward the center of the dimer (discussed below). Remarkably, the residues near Val38 were predicted successfully to be a putative ligand-binding site for BARF1 by structural comparison alone (18). However, the utilization of the flipped Val38, rather than the exposed Trp35/Val38/Leu40/Leu108 hydrophobic area, as an insert in ligand binding was unexpected.…”

Section: Resultsmentioning

confidence: 99%

“…Other studies have suggested that BARF1 may work as a survival factor, most likely by inhibiting apoptosis (17), and it also was suggested that the antiproliferative action of BARF1 may be caused by sequestration of the ligand by binding to the receptorbinding site of the ligand (13,18). In all functional roles, it is suggested that BARF1 binds M-CSF competitively, and in fact it has been demonstrated that BARF1 interacts with all isoforms of M-CSF (soluble or membrane spanning) (13).…”

mentioning

confidence: 99%

“…The crystal structure of free BARF1 has been determined and shows that BARF1 oligomerizes into a hexameric ring (18), but how the hexameric BARF1 engages M-CSF, a dimeric cytokine with a four-helix bundle scaffold (16,19), has been a perplexing question. How the competition between BARF1 and FMS, the cognate M-CSF receptor, is achieved also has been unclear.…”

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confidence: 99%

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Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein–Barr virus BARF1

Shim¹,

Chang

Chen³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein–Barr virus BARF1

Shim¹,

Chang

Chen³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…La mononucleosis es la principal infección causada por EBV, la cual se desarrolla en la adolescencia y en edad adulta (Tarbouriech et al, 2006). Su genoma se representa como una molécula lineal de DNA bicatenario (172kb), con repeticiones reiteradas terminales de 0,5 kb y repeticiones reiteradas internas directa de 3 kb (Middeldorp et al, 2003).…”

Section: Virus Epstein-barr (Ebv) El Virus De Epstein-barr (Ebv)unclassified

Infecciones de Transmisión Sexual en Semen: El Hombre como Vector de Transmisión

Andana

et al. 2013

Int. J. Morphol.

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RESUMEN:En los últimos años el estudio de las infecciones de transmisión sexual ha cobrado gran importancia debido principalmente al incremento de estas en parejas heterosexuales y hombres que tienen sexo con hombres. En mujeres existe mucha información de epidemiología y patogénesis de estas infecciones, sin embargo, en hombres la información es muy escasa debido a que la mayoría no presenta sintomatología. En los últimos años se ha evidenciado un creciente interés en el estudio del semen como vía de transmisión, debido principalmente a la afinidad de algunos patógenos con los espermatozoides. Dentro de los principales microorganismos infectantes en semen se encuentran Chlamydia trachomatis, Neisseria gonorrhoeae, Mollicutes, Virus de la Inmunodeficiencia Humana tipos 1 y 2, Virus Herpes Simplex 1 y 2, Virus Papiloma Humano, Virus de la Hepatitis B y C, Citomegalovirus, Virus Epstein-Barr y Trichomonas vaginalis.PALABRAS CLAVE: Infecciones de transmisión sexual; Semen; Virus; Bacterias; Protozoos. INTRODUCCIÓNEn los últimos años se han incrementado los casos de enfermedades de transmisión sexual, debido principalmente al aumento en el número de compañeros sexuales en parejas heterosexuales y de hombres que tienen sexo con hombres (HSH), lo que hace aún más factible y rápida su propagación (Apers et al., 2012). Los principales riesgos asociados son daños irreparables en los hijos de madres infectadas durante la gestación o el nacimiento, entre éstos, ceguera, deformidades óseas, retraso mental e inclusive la muerte. Además, en las mujeres pueden causar enfermedad inflamatoria pélvica, infertilidad, embarazos ectópicos potencialmente mortales y cáncer en el aparato reproductor (Gupta & Bowman, 2012). En hombres la infección está asociada a tumores de piel, región perianal, tonsila, orofaringe, laringe, esófago, próstata y uretra (Giuliano et al., 2008). La principal forma de transmisión de estos microorganismos son las relaciones sexuales sin protección, ya sea por vía vaginal, oral o anal. El semen es susceptible de ser infectado por varios microorganismos, como bacterias, virus y protozoos, los cuales encuentran en el plasma seminal las condiciones óptimas para su supervivencia (Shim, 2011). El semen contiene una heterogeneidad de componentes: A) fracción celular: células espermáticas, leucocitos y células epiteliales, y B) fracción plasmática (Dejucq-Rainsford & Jegou, 2001). Los espermatozoides pueden infectarse en el epidídimo, conducto deferente o uretra. Los microorganismos pueden estar presentes en el semen y asociarse con espermatozoides y/o otras células presentes en el líquido seminal como leucocitos, células epiteliales, glóbulos rojos, etc., especialmente cuando existe algún tipo de inflamación o trauma de las glándulas sexuales accesorias (próstata, vesícula seminal, o glándula bulbouretral) (Dejucq-Rainsford & Jegou, 2004

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Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion

et al. 2017

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Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools.

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Structure of the Epstein-Barr Virus Oncogene BARF1

Cited by 43 publications

References 49 publications

Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein–Barr virus BARF1

Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein–Barr virus BARF1

Infecciones de Transmisión Sexual en Semen: El Hombre como Vector de Transmisión

Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion

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