Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice.

The lymphoma-inducing potential of Ig heavy-chain enhancer- and promoter-regulated Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) was evaluated in three transgenic FVB mouse lineages. EBNA1 was expressed at a higher level in transgenic B220(+) splenocytes than in EBV-infected lymphoblastoid cell lines. EBNA1 was also expressed in B220(-) transgenic splenocytes and thymocytes. Before killing and assessments at 18-26 months, EBNA1-transgenic mice did not differ from control mice in mortality. At 18-26 months EBNA1-transgenic mice did not differ from littermate control in ultimate body weight, in spleen size or weight, in lymph node, kidney, liver, or spleen histology, in splenocyte fractions positive for cluster of differentiation (CD)3epsilon, CD4, CD8, CD62L, B220, CD5, IgM, IgD, MHC class II, CD11b, or CD25, or in serum IgM, IgG, or total Ig levels. Lymphomas were not found in spleens or other organs of 18- to 26-month-old EBNA1-transgenic (n=86) or control (n=45) FVB mice. EBNA1-transgenic lineages had a higher pulmonary adenoma prevalence than did littermate controls (39% versus 7%). However, the adenoma prevalence was not higher in EBNA1-transgenic mice than has been described for FVB mice, and EBNA1 was not expressed in normal pulmonary epithelia or adenomas.

[1]  E. Kieff,et al.  Epstein–Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKKα-dependent noncanonical NF-κB activation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Katherine Luzuriaga,et al.  Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Arrowsmith,et al.  Protein Interaction Domains of the Ubiquitin-specific Protease, USP7/HAUSP* , 2003, Journal of Biological Chemistry.

[4]  B. Sugden,et al.  Epstein-Barr virus provides a survival factor to Burkitt's lymphomas , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Sugden,et al.  EBNA-1, a Bifunctional Transcriptional Activator , 2003, Molecular and Cellular Biology.

[6]  R. Küppers B cells under influence: transformation of B cells by Epstein–Barr virus , 2003, Nature Reviews Immunology.

[7]  W. Hammerschmidt,et al.  The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Greenblatt,et al.  Protein Profiling with Epstein-Barr Nuclear Antigen-1 Reveals an Interaction with the Herpesvirus-associated Ubiquitin-specific Protease HAUSP/USP7* , 2003, Journal of Biological Chemistry.

[9]  L. Frappier,et al.  EBNA1 Partitions Epstein-Barr Virus Plasmids in Yeast Cells by Attaching to Human EBNA1-Binding Protein 2 on Mitotic Chromosomes , 2003, Journal of Virology.

[10]  Ying-Chu Lee,et al.  The Epstein–Barr virus nuclear antigen‐1 may act as a transforming suppressor of the HER2/neu oncogene , 2002, FEBS letters.

[11]  K. Yamamura,et al.  Strain‐dependency of Chromosomal Abnormalities in Lymphomas Developed in Eμ‐myc Transgenic Mice , 2002, Japanese journal of cancer research : Gann.

[12]  E. Kieff,et al.  Epstein–Barr virus nuclear antigen 1 activates transcription from episomal but not integrated DNA and does not alter lymphocyte growth , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Hearing,et al.  The Replicator of the Epstein-Barr Virus Latent Cycle Origin of DNA Replication, oriP, Is Composed of Multiple Functional Elements , 2001, Journal of Virology.

[14]  L. Frappier,et al.  The Budding Yeast Homolog of the Human EBNA1-binding Protein 2 (Ebp2p) Is an Essential Nucleolar Protein Required for Pre-rRNA Processing* , 2000, The Journal of Biological Chemistry.

[15]  A. Krainer,et al.  Human p32: a coactivator for Epstein-Barr virus nuclear antigen-1-mediated transcriptional activation and possible role in viral latent cycle DNA replication. , 2000, Virology.

[16]  Aled M. Edwards,et al.  Two Domains of the Epstein-Barr Virus Origin DNA-binding Protein, EBNA1, Orchestrate Sequence-specific DNA Binding* , 2000, The Journal of Biological Chemistry.

[17]  J. Babbitt,et al.  Hematopoietic neoplasia in C57BL/6 mice exposed to split-dose ionizing radiation and circularly polarized 60 Hz magnetic fields. , 2000, Carcinogenesis.

[18]  S. Maruo,et al.  Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata , 1999, Journal of Virology.

[19]  T. Piolot,et al.  Mapping EBNA-1 Domains Involved in Binding to Metaphase Chromosomes , 1999, Journal of Virology.

[20]  B. Sugden,et al.  The Linking Regions of EBNA1 Are Essential for Its Support of Replication and Transcription , 1999, Molecular and Cellular Biology.

[21]  J. Yates,et al.  Genetic Evidence that EBNA-1 Is Needed for Efficient, Stable Latent Infection by Epstein-Barr Virus , 1999, Journal of Virology.

[22]  J. Pagano,et al.  Expression of EBNA-1 mRNA Is Regulated by Cell Cycle during Epstein-Barr Virus Type I Latency , 1999, Journal of Virology.

[23]  J. Sample,et al.  Epstein-Barr Virus Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt Lymphoma , 1999, Molecular and Cellular Biology.

[24]  V. Diehl,et al.  Expression of Epstein-Barr Virus Nuclear Antigen 1 Is Associated with Enhanced Expression of CD25 in the Hodgkin Cell Line L428 , 1999, Journal of Virology.

[25]  K. Takada,et al.  Epstein-Barr Virus Contributes to the Malignant Phenotype and to Apoptosis Resistance in Burkitt’s Lymphoma Cell Line Akata , 1998, Journal of Virology.

[26]  M. O’Donnell,et al.  Human RPA (hSSB) interacts with EBNA1, the latent origin binding protein of Epstein-Barr virus. , 1998, Nucleic acids research.

[27]  B. Sugden,et al.  Studies on the Mechanism of DNA Linking by Epstein-Barr Virus Nuclear Antigen 1* , 1997, The Journal of Biological Chemistry.

[28]  A Ciechanover,et al.  Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Jaap M Middeldorp,et al.  P32/TAP, a cellular protein that interacts with EBNA-1 of Epstein-Barr virus. , 1997, Virology.

[30]  G. Nemerow,et al.  Growth arrest of Epstein-Barr virus immortalized B lymphocytes by adenovirus-delivered ribozymes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[31]  I. Miyoshi,et al.  Differential tumorigenicity between Epstein-Barr virus genome-positive and genome-negative cell lines with t(11;14)(q13;q32) derived from mantle cell lymphoma , 1996, Journal of virology.

[32]  R. Maronpot,et al.  Spontaneous Lesions in Aging FVB/N Mice , 1996, Toxicologic pathology.

[33]  A. Levine,et al.  Expression of Epstein‐Barr virus nuclear antigen‐1 induces B cell neoplasia in transgenic mice. , 1996, The EMBO journal.

[34]  R. Pfuetzner,et al.  Crystal Structure of the DNA-Binding Domain of the Epstein–Barr Virus Origin-Binding Protein, EBNA1, Bound to DNA , 1996, Cell.

[35]  Stefan Imreh,et al.  Inhibition of antigen processing by the internal repeat region of the Epstein–Barr virus nuclear antigen-1 , 1995, Nature.

[36]  B. Sugden,et al.  An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein-Barr virus LMP gene , 1995, Journal of virology.

[37]  P. Farrell,et al.  Novel hypotheses for the roles of EBNA-1 and BHRF1 in EBV-related cancers. , 1995, Intervirology.

[38]  G. Freeman,et al.  A negative regulatory function of B7 revealed in B7-1 transgenic mice. , 1994, Immunity.

[39]  L. Frappier,et al.  Identification of EBNA1 amino acid sequences required for the interaction of the functional elements of the Epstein-Barr virus latent origin of DNA replication , 1993, Journal of virology.

[40]  J. Miyazaki,et al.  Strain Dependency of Cell‐type Specificity and Onset of Lymphoma Development in Eμ‐myc Transgenic Mice , 1992, Japanese journal of cancer research : Gann.

[41]  G. Hayward,et al.  Functional domains of Epstein-Barr virus nuclear antigen EBNA-1 , 1991, Journal of virology.

[42]  G. Hayward,et al.  Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA , 1990, Journal of virology.

[43]  K. Yamamura,et al.  Strain dependency of B and T lymphoma development in immunoglobulin heavy chain enhancer (E mu)-myc transgenic mice , 1989, The Journal of experimental medicine.

[44]  J. Yates,et al.  Multiple EBNA1-binding sites are required to form an EBNA1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus , 1989, Journal of virology.

[45]  E. Newcomb,et al.  Pathogenesis of Burkitt lymphoma: Expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts , 1987, Cell.

[46]  D. Reisman,et al.  trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1 , 1986, Molecular and cellular biology.

[47]  M. Potter,et al.  Mechanisms in B-cell neoplasia. Workshop at the National Cancer Institute, National Institutes of Health. Bethesda, MD, USA, March 24-26, 1986. , 1986, Current topics in microbiology and immunology.

[48]  D. Volsky,et al.  Transfer of the Epstein-Barr virus (EBV) DNA fragment coding for EBNA-1, the putative transforming antigen of EBV, into normal human lymphocytes: gene expression without cell transformation. , 1986, Biochemical and biophysical research communications.

[49]  R. Palmiter,et al.  c-myc-induced lymphomagenesis in transgenic mice and the role of the Pvt-1 locus in lymphoid neoplasia. , 1986, Current topics in microbiology and immunology.

[50]  R. Palmiter,et al.  The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice , 1985, Nature.

[51]  G. Hayward,et al.  Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region , 1985, Cell.

[52]  J. Yates,et al.  Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells , 1985, Nature.

[53]  P. L. Deininger,et al.  DNA sequence and expression of the B95-8 Epstein—Barr virus genome , 1984, Nature.

[54]  D. Reisman,et al.  A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.