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PMID: 2849118 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency.

Rooney C, Taylor N, Countryman J, Jenson H, Kolman J, Miller G

Abstract

A defective Epstein-Barr virus (EBV) containing a deleted and rearranged genome (het DNA) causes latent EBV to replicate. This activity maps to the 2.7-kilobase-pair WZhet fragment. The BZLF1 open reading frame, present within WZhet as well as in the standard viral BamHI Z fragment, encodes the protein ZEBRA, which induces viral replication. Using gene transfers into Burkitt lymphoma cells, we now demonstrate that rearranged sequences juxtaposed to BZLF1 in het DNA facilitate expression of ZEBRA protein. Two stretches of EBV sequences within a palindromic region of het DNA contain positive regulatory elements. One set, derived from the viral large internal repeat, is newly positioned upstream of BZLF1; the second set is downstream of BZLF1 in het DNA. The capacity of defective HR-1 viruses to disrupt latency of the standard EBV genome is due to abnormal regulation of the BZLF1 gene as a result of genomic rearrangements.

MeSH Terms
Base Sequence Cell Line Chromosome Deletion Deoxyribonuclease EcoRI/metabolism Enhancer Elements, Genetic Gene Expression Regulation Herpesvirus 4, Human/genetics Promoter Regions, Genetic Simian virus 40/genetics Transfection Viral Proteins/genetics Virus Replication
Chemicals
Viral Proteins Deoxyribonuclease EcoRI
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rooney C
Department of Epidemiology, Yale University School of Medicine, New Haven, CT 06510.
Taylor N
Countryman J
Jenson H
Kolman J
Miller G
References (36)
36 references, click to expand
  1. Tumor initiators and promoters in the induction of Epstein-Barr virus.
    Proc Natl Acad Sci U S A. 1979 Feb;76(2):782-5 PMID: 218219
  2. Polymorphisms of the region of the Epstein-Barr virus genome which disrupts latency.
    Virology. 1988 Aug;165(2):549-64 PMID: 2841800
  3. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):805-9 PMID: 6262773
  4. Epstein-Barr virus RNA. VIII. Viral RNA in permissively infected B95-8 cells.
    J Virol. 1982 Jul;43(1):262-72 PMID: 6180174
  5. An unusually high-titer human anti-Epstein Barr virus (EBV) serum and its use in the study of EBV-specific proteins synthesized in vitro and in vivo.
    J Immunol. 1983 Feb;130(2):919-24 PMID: 6294181
  6. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye.
    J Virol. 1982 Dec;44(3):834-44 PMID: 6294333
  7. Identification of a rare Epstein-Barr virus variant that enhances early antigen expression in Raji cells.
    Proc Natl Acad Sci U S A. 1983 May;80(9):2762-6 PMID: 6302703
  8. Identification of Epstein-Barr nuclear antigen polypeptide in mouse and monkey cells after gene transfer with a cloned 2.9-kilobase-pair subfragment of the genome.
    Proc Natl Acad Sci U S A. 1984 Jan;81(1):43-7 PMID: 6320171
  9. Epstein-Barr virus with heterogeneous DNA disrupts latency.
    J Virol. 1984 Apr;50(1):174-82 PMID: 6321789
  10. Structure of defective DNA molecules in Epstein-Barr virus preparations from P3HR-1 cells.
    J Virol. 1984 Jul;51(1):199-207 PMID: 6328039
  11. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein.
    J Virol. 1984 Aug;51(2):411-9 PMID: 6086953
  12. Spliced RNA from the IR1-U2 region of Epstein-Barr virus: presence of an open reading frame for a repetitive polypeptide.
    EMBO J. 1984 Aug;3(8):1913-7 PMID: 6090131
  13. Latent and viral replicative transcription in vivo from the BamHI K fragment of Epstein-Barr virus DNA.
    J Virol. 1985 May;54(2):501-8 PMID: 2985812
  14. Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4085-9 PMID: 2987963
  15. Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells.
    J Virol. 1985 Sep;55(3):710-20 PMID: 2991591
  16. Identification and expression of a nuclear antigen from the genomic region of the Jijoye strain of Epstein-Barr virus that is missing in its nonimmortalizing deletion mutant, P3HR-1.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7429-33 PMID: 2997790
  17. trans activation of the latent Epstein-Barr virus (EBV) genome after transfection of the EBV DNA fragment.
    J Virol. 1986 Mar;57(3):1016-22 PMID: 3005608
  18. Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells.
    Proc Natl Acad Sci U S A. 1986 Mar;83(5):1499-503 PMID: 3485288
  19. Palindromic structure and polypeptide expression of 36 kilobase pairs of heterogeneous Epstein-Barr virus (P3HR-1) DNA.
    J Virol. 1986 May;58(2):475-86 PMID: 3009861
  20. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site.
    Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096-100 PMID: 3460083
  21. Definitive identification of a member of the Epstein-Barr virus nuclear protein 3 family.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5693-7 PMID: 3016714
  22. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  23. Promiscuous trans activation of gene expression by an Epstein-Barr virus-encoded early nuclear protein.
    J Virol. 1986 Oct;60(1):140-8 PMID: 3018281
  24. Identification and mapping of Epstein-Barr virus early antigens and demonstration of a viral gene activator that functions in trans.
    J Virol. 1986 Oct;60(1):149-56 PMID: 3018282
  25. Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer.
    Nature. 1986 Oct 9-15;323(6088):555-8 PMID: 3020435
  26. An Epstein-Barr virus transcript from a latently infected, growth-transformed B-cell line encodes a highly repetitive polypeptide.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9298-302 PMID: 3025831
  27. Novel nuclear antigens recognized by human sera in lymphocytes latently infected by Epstein-Barr virus.
    Virology. 1987 Jan;156(1):153-62 PMID: 3027963
  28. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter.
    EMBO J. 1986 Dec 1;5(12):3243-9 PMID: 3028777
  29. Transfection of a rearranged viral DNA fragment, WZhet, stably converts latent Epstein-Barr viral infection to productive infection in lymphoid cells.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1332-6 PMID: 3029778
  30. Sequences of the Epstein-Barr Virus (EBV) large internal repeat form the center of a 16-kilobase-pair palindrome of EBV (P3HR-1) heterogeneous DNA.
    J Virol. 1987 May;61(5):1495-506 PMID: 3033277
  31. Two strains of Epstein-Barr virus (B95-8 and a P3HR-1 subclone) that lack defective genomes induce early antigen and cause abortive infection of Raji cells.
    J Virol. 1987 Jun;61(6):1985-91 PMID: 3033325
  32. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements.
    Cell. 1987 Jun 19;49(6):741-52 PMID: 3034433
  33. Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency.
    J Virol. 1987 Dec;61(12):3672-9 PMID: 2824806
  34. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060-4 PMID: 2825176
  35. A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome.
    EMBO J. 1988 Mar;7(3):769-74 PMID: 2840285
  36. Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate.
    Virology. 1979 Apr 15;94(1):228-31 PMID: 220786
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
Published
1988-12-00
Pages
9801-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC282869
Subset
IM
Grants
NCI NIH HHS · CA12055 · United States
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