Try out PMC Labs and tell us what you think. Learn More. EBNA-1 binds in a site-specific manner to the viral DNA and is essential for viral replication, as well as for maintaining the genome as an extrachromosomal episome within infected cells. EBNA-1 is not recognized by the cellular immune system. We also show that EBNA-1 can bind exon sequences derived from its own RNA expressed from the Fp promoter, as found in Burkitt's lymphoma-related cells and in nasopharyngeal carcinomas. Full text is available as a scanned copy of the original print version.
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National Center for Biotechnology Information , U. EMBO J. Author information Copyright and License information Disclaimer. Copyright notice. This article has been cited by other articles in PMC. Images in this article Image on p. Image on p. J Virol. Nucleic Acids Res. The glycine-alanine domain minimizes translation, binds to proteasomes and inhibits EBNA-1 proteolysis. EBNA-1 a. The key LMP-1 functional domains are: i six transmembrane domains TM1—6 , which mediate raft association, constitutive aggregation and constitutive signaling; and ii two transformation effector sites TES1 and TES2.
LMP-1 oligomerizes on the plasma membrane through TM1 interaction with TM3—6, forming a ligand-independent signaling complex. LMP-2A promotes B-cell growth, 62 induces B lymphoma, has a transformation ability in vitro and in vivo , which was blocked by an immunoreceptor tyrosine-based activation motif LMP-2A mutant, the Syk inhibitor or Syk-specific small interfering RNA, and is important but not essential for in vitro primary B-lymphocyte growth transformation, latent infection and lytic virus replication in vitro 43 , , but is essential for growth transformation of germinal center B cells, which do not express the genuine BCR because of deleterious somatic hypermutations in their immunoglobulin genes; it increases the prosurvival and anti-inflammatory cytokine IL via PI3K, upregulates genes associated with cell cycle induction and inhibition of apoptosis and downregulates genes associated with B-cell-specific factors and immunity similarly to those in HRS cells of HL, and it counteracts the antiproliferative effect of the S10A mutant to promote the S-phase entry.
EBNA-3C functions as a coactivator and corepressor. EBNA-3A represses contiguous clusters arrayed in the human genome by polycomb group-mediated epigenetic silencing. A Bim is a cellular inducer of apoptosis. The expression of chemokine CXCL12 and its receptor contributes to EBV-positive peripheral blood mononuclear cell growth in mice with severe combined immunodeficiency disease.
National Center for Biotechnology Information , U. Journal List Exp Mol Med v. Exp Mol Med. Published online Jan Author information Article notes Copyright and License information Disclaimer. E-mail: ude. Received Sep 16; Accepted Oct 1. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
This article has been cited by other articles in PMC. Introduction A physican by name Burkitt was the first to describe a unique lymphoma. Table 1 Roles of EBV-encoded latent genes. Open in a separate window. LMP1 structure, domain and interactions The key LMP-1 functional domains are: i six transmembrane domains TM1—6 , which mediate raft association, constitutive aggregation and constitutive signaling; and ii two transformation effector sites TES1 and TES2.
Figure 1. Notes The authors declare no conflict of interest. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. Observations on childhood infections with the Epstein—Barr virus. J Infect Dis. Antibodies to Epstein—Barr virus in Burkitt's lymphoma and control groups.
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Final case reporting from the Ugandan prospective study of the relationship between EBV and Burkitt's lymphoma. Int J Cancer. Replication of Epstein—Barr virus in human epithelial cells infected in vitro. Epstein—Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. A second site for Epstein—Barr virus shedding: the uterine cervix. A transformation-incompetent, nuclear antigen 2-deleted Epstein—Barr virus associated with replicative infection.
Epithelial cell polarization is a determinant in the infectious outcome of immunoglobulin A-mediated entry by Epstein—Barr virus.
J Virol. Epstein—Barr virus infection in ex vivo tonsil epithelial cell cultures of asymptomatic carriers. Epstein—Barr virus receptors on human pharyngeal epithelia.
Differentiation-associated expression of the Epstein—Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia. Oral Dis. Epstein—Barr virus coinfection and recombination in non-human immunodeficiency virus-associated oral hairy leukoplakia. Hairy leukoplakia: an unusual combination of transforming and permissive Epstein—Barr virus infections.
Expression of Epstein—Barr virus latent genes in oral epithelium: determinants of the pathogenesis of oral hairy leukoplakia. Epstein—Barr virus infection of Langerhans cell precursors as a mechanism of oral epithelial entry, persistence, and reactivation. Epstein—Barr virus genomes with properties of circular DNA molecules in carrier cells.
J Pathol. Immunohistochemical detection of the Epstein—Barr virus-encoded latent membrane protein 2A in Hodgkin's disease and infectious mononucleosis. Epstein—Barr virus EBV in infectious mononucleosis: detection of the virus in tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells.
Mol Pathol. Epstein—Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction. Peripheral B cells latently infected with Epstein—Barr virus display molecular hallmarks of classical antigen-selected memory B cells.
Terminal differentiation into plasma cells initiates the replicative cycle of Epstein—Barr virus in vivo. J Immunol. Eur J Cancer Clin Oncol. Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Establishment of cell lines from peripheral leukocytes in infectious mononucleosis. Transformation of huiman foetal leukocytes in vitro by filtrates of a human leukaemic line containing herpes-like virus.
Early events in Epstein—Barr virus infection of human B lymphocytes. Epstein—Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation. Epstein—Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein—Barr virus latent membrane protein 2 LMP2 are dispensable for lymphocyte infection and growth transformation in vitro.
Epstein—Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa. Use of second-site homologous recombination to demonstrate that Epstein—Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro. Epstein—Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. An Epstein—Barr virus that expresses only the first LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation.
The Epstein—Barr virus LMP1 cytoplasmic carboxy terminus is essential for B-lymphocyte transformation; fibroblast cocultivation complements a critical function within the terminal residues. The residues between the two transformation effector sites of Epstein—Barr virus latent membrane protein 1 are not critical for B-lymphocyte growth transformation.
Mol Cell Biol. Epstein—Barr virus recombinant molecular genetic analysis of the LMP1 amino-terminal cytoplasmic domain reveals a probable structural role, with no component essential for primary B-lymphocyte growth transformation. The Epstein—Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation.
The Epstein—Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF- kappaB. These interventions make the described method more efficient, resulting in rapid expansion of cells for subsequent experiments. Traditionally, growth transformation has been monitored by visualization of clusters of cells by light microscopy about a week after exposure to EBV 6, However, clustering of cells is not a specific indicator of EBV-mediated growth transformation.
We have previously demonstrated consistent identification of the proliferating cell population via flow cytometry 14 , providing an accurate and specific method to determine successful outcome as early as three days after exposure of B cells to EBV. Hood Foundation to S. National Center for Biotechnology Information , U. J Vis Exp. Published online Nov 8. Author information Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Download video file. Protocol 1. Isolation of peripheral blood mononuclear cells PBMC Draw 10 ml blood from donor into a heparinized syringe or a heparinized blood tube.
Expansion and cryopreservation of LCL Visualization of cells by light microscopy: By a week after EBV infection, clusters of cells are visible by light microscopy. Discussion The method described in this paper generates LCL from donor peripheral blood with rapid immortalization and cryopreservation times.
Disclosures No conflicts of interest declared. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. Use of spontaneous Epstein-Barr virus lymphoblastoid cell lines genetically modified to express tumor antigen as cancer vaccines: mutated p21 ras oncogene in pancreatic carcinoma as a model.
Gene Ther. B cells under influence: transformation of B cells by Epstein-Barr virus. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Maintenance of serological memory by polyclonal activation of human memory B cells. An efficient method for the rapid establishment of Epstein-Barr virus immortalization of human B lymphocytes.
Cell Prolif. Use of a simple method for the Epstein-Barr virus transformation of lymphocytes from members of large families of Reunion Island. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Characteristics of Epstein-Barr virus activation of human B lymphocytes.
A routine method for the establishment of permanent growing lymphoblastoid cell lines. Human B lymphocytes immortalization by Epstein-Barr virus in the presence of cyclosporin A. In Vitro Cell Dev. Epstein-Barr virus transformation of cryopreserved lymphocytes: prolonged experience with technique. Epstein-Barr virus: Transformation, cytopathic changes, and viral antigens in squirrel monkey and marmoset leukocytes.
Identification of a sub-population of B cells that proliferates after infection with Epstein-Barr virus.
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