Home LiteratureArticle Details
PMID: 14603034 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus provides a survival factor to Burkitt's lymphomas.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 24 ·2003-11-25 ·Pages 14269-74

Kennedy G, Komano J, Sugden B

Abstract

Epstein-Barr virus (EBV) has been causally associated with at least five human malignancies. The exact contributions made by EBV to these cancers remain unknown. We demonstrate that one viral protein found in all EBV-associated malignancies, Epstein-Barr nuclear antigen 1 (EBNA-1), is required for survival of one of these cancers, EBV-positive Burkitt's lymphoma. Inhibition of EBNA-1 decreases survival of these tumor cells by inducing apoptosis. Expression of EBNA-1 in uninfected cells also can inhibit apoptosis induced by expression of p53 in the absence of the EBV genome. Our findings demonstrate that EBNA-1 is critical for the continued survival of EBV-associated Burkitt's lymphoma, and, by extension, for the other B cell tumors with which EBV is associated. Efficient inhibitors of EBNA-1's functions would likely prove useful in the therapy of EBV-associated malignancies.

MeSH Terms
Apoptosis B-Lymphocytes/pathology,virology Burkitt Lymphoma/pathology,virology Cell Line Cell Survival Epstein-Barr Virus Nuclear Antigens/genetics,physiology Genome, Viral Herpesvirus 4, Human/genetics,pathogenicity,physiology Humans Sequence Deletion Transduction, Genetic
Chemicals
Epstein-Barr Virus Nuclear Antigens EBV-encoded nuclear antigen 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kennedy Gregory
McArdle Laboratory for Cancer Research and Department of Surgery, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Komano Jun
Sugden Bill
References (42)
42 references, click to expand
  1. EBV persistence in memory B cells in vivo.
    Immunity. 1998 Sep;9(3):395-404 PMID: 9768759
  2. Interferon-independent and -induced regulation of Epstein-Barr virus EBNA-1 gene transcription in Burkitt lymphoma.
    J Virol. 1997 Sep;71(9):6887-97 PMID: 9261415
  3. Epstein-barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma.
    Mol Cell Biol. 1999 Mar;19(3):1651-60 PMID: 10022853
  4. The linking regions of EBNA1 are essential for its support of replication and transcription.
    Mol Cell Biol. 1999 May;19(5):3349-59 PMID: 10207059
  5. A new tumour-derived transforming strain of Epstein-Barr virus.
    Nature. 1978 Apr 13;272(5654):629-31 PMID: 205793
  6. Epstein-Barr virus DNA is amplified in transformed lymphocytes.
    J Virol. 1979 Sep;31(3):590-5 PMID: 229241
  7. Mitotic EBNA-positive lymphocytes in peripheral blood during infectious mononucleosis.
    Nature. 1980 Sep 25;287(5780):334-5 PMID: 6252472
  8. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):4251-5 PMID: 6933474
  9. Major EB virus-specific cytoplasmic transcripts in a cellular clone of the HR-1 Burkitt lymphoma line during latency and after induction of viral replicative cycle by phorbol esters.
    Virology. 1983 Mar;125(2):287-98 PMID: 6301144
  10. Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells.
    J Virol. 1987 May;61(5):1310-7 PMID: 3033261
  11. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells.
    EMBO J. 1987 Sep;6(9):2743-51 PMID: 2824192
  12. The average number of molecules of Epstein-Barr nuclear antigen 1 per cell does not correlate with the average number of Epstein-Barr virus (EBV) DNA molecules per cell among different clones of EBV-immortalized cells.
    J Virol. 1990 May;64(5):2407-10 PMID: 2157896
  13. An Epstein-Barr virus-producer line Akata: establishment of the cell line and analysis of viral DNA.
    Virus Genes. 1991 Apr;5(2):147-56 PMID: 1647567
  14. p53 is frequently mutated in Burkitt's lymphoma cell lines.
    EMBO J. 1991 Oct;10(10):2879-87 PMID: 1915267
  15. Human B-lymphoid cell lines.
    Hum Cell. 1992 Mar;5(1):25-41 PMID: 1329931
  16. The p53-mdm-2 autoregulatory feedback loop.
    Genes Dev. 1993 Jul;7(7A):1126-32 PMID: 8319905
  17. p53 and E2F-1 cooperate to mediate apoptosis.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602-6 PMID: 8170954
  18. Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt's lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV.
    J Virol. 1994 Sep;68(9):6069-73 PMID: 8057484
  19. Clonal propagation of Epstein-Barr virus (EBV) recombinants in EBV-negative Akata cells.
    J Virol. 1996 Oct;70(10):7260-3 PMID: 8794379
  20. Evidence for a large compartment of IgM-expressing memory B cells in humans.
    Blood. 1997 Feb 15;89(4):1288-98 PMID: 9028952
  21. Dominant-negative inhibitors of EBNA-1 of Epstein-Barr virus.
    J Virol. 1997 Mar;71(3):1766-75 PMID: 9032305
  22. The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen.
    J Virol. 1997 Aug;71(8):5915-21 PMID: 9223481
  23. Oncogenic role of Epstein-Barr virus-encoded RNAs in Burkitt's lymphoma cell line Akata.
    J Virol. 1999 Dec;73(12):9827-31 PMID: 10559294
  24. p53 inhibition by the LANA protein of KSHV protects against cell death.
    Nature. 1999 Dec 23-30;402(6764):889-94 PMID: 10622254
  25. EBNA-1: a protein pivotal to latent infection by Epstein-Barr virus.
    Rev Med Virol. 2000 Mar-Apr;10(2):83-100 PMID: 10713596
  26. Rapid induction of senescence in human cervical carcinoma cells.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10978-83 PMID: 11005870
  27. Epstein-Barr virus-encoded poly(A)(-) RNA supports Burkitt's lymphoma growth through interleukin-10 induction.
    EMBO J. 2000 Dec 15;19(24):6742-50 PMID: 11118209
  28. p14ARF homozygous deletion or MDM2 overexpression in Burkitt lymphoma lines carrying wild type p53.
    Oncogene. 2001 Apr 19;20(17):2171-7 PMID: 11360201
  29. Epstein-Barr virus infection and human malignancies.
    Int J Exp Pathol. 2001 Jun;82(3):149-70 PMID: 11488990
  30. Translocations involving c-myc and c-myc function.
    Oncogene. 2001 Sep 10;20(40):5595-610 PMID: 11607812
  31. Induced senescence in HeLa cervical carcinoma cells containing elevated telomerase activity and extended telomeres.
    Cell Growth Differ. 2001 Nov;12(11):525-34 PMID: 11714633
  32. Epstein-Barr virus nuclear antigen 1 activates transcription from episomal but not integrated DNA and does not alter lymphocyte growth.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15233-8 PMID: 11734622
  33. Separation of the DNA replication, segregation, and transcriptional activation functions of Epstein-Barr nuclear antigen 1.
    J Virol. 2002 Mar;76(5):2480-90 PMID: 11836426
  34. Epstein-Barr virus RNA confers resistance to interferon-alpha-induced apoptosis in Burkitt's lymphoma.
    EMBO J. 2002 Mar 1;21(5):954-65 PMID: 11867523
  35. Burkitt's and Burkitt-like lymphoma.
    Curr Treat Options Oncol. 2002 Aug;3(4):291-305 PMID: 12074766
  36. Role of genetic and epigenetic changes in Burkitt lymphoma.
    Semin Cancer Biol. 2002 Oct;12(5):381-7 PMID: 12191637
  37. Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2.
    Nat Med. 2002 Oct;8(10):1098-104 PMID: 12219084
  38. The life and death of a B cell.
    Adv Cancer Res. 2002;86:195-225 PMID: 12374279
  39. EBNA-1, a bifunctional transcriptional activator.
    Mol Cell Biol. 2003 Oct;23(19):6901-8 PMID: 12972608
  40. Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas.
    Proc Natl Acad Sci U S A. 1974 Aug;71(8):3283-6 PMID: 4369887
  41. Establishment in continuous culture of a new type of lymphocyte from a "Burkitt like" malignant lymphoma (line D.G.-75).
    Int J Cancer. 1977 Jan;19(1):27-33 PMID: 188769
  42. Epstein-Barr virus contributes to the malignant phenotype and to apoptosis resistance in Burkitt's lymphoma cell line Akata.
    J Virol. 1998 Nov;72(11):9150-6 PMID: 9765461
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.2336099100
Published
2003-11-25
Epub
2003-00-05
Pages
14269-74
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC283581
Subset
IM
Grants
NCI NIH HHS · T32-CA-009614-13 · United States
NCI NIH HHS · T32 CA009614 · United States
NCI NIH HHS · CA-22443 · United States
NCI NIH HHS · P01 CA022443 · United States
NCI NIH HHS · CA-07175 · United States
External Links
PubMed source DOI: 10.1073/pnas.2336099100 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2