An EBNA-1-dependent Enhancer Acts from a Distance of 10 Kilobase Pairs to Increase Expression of the Epstein-Barr Virus LMP Gene

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1995 Apr 1

PMID 7884916

Citations 85

Authors

T A Gahn

B Sugden

Affiliations

Soon will be listed here.

Abstract

Upon infection of human B lymphocytes, the 172-kbp Epstein-Barr virus genome forms a covalently closed circle via its terminal repeats. This event brings all of the promoters that control expression of the latent gene products, and the viral origin of plasmid replication, oriP, within a 20-kbp stretch of contiguous DNA. We have found that the EBNA-1-dependent transcriptional enhancer FR, located in oriP, increased the expression of a tagged viral oncogene encoding the latent membrane protein (LMP) up to 200-fold in normal Epstein-Barr virus-positive cells. The effect of FR was exerted across 10 kbp of viral DNA that spans the circularized ends of the viral genome. Enhancement of the tagged LMP gene by FR/EBNA-1 did not require the EBNA-2-responsive element.

Citing Articles

Peptides for microbe-induced cancers: latest therapeutic strategies and their advanced technologies.

Lin Z, Assaraf Y, Kwok H Cancer Metastasis Rev. 2024; 43(4):1315-1336.

PMID: 39008152 DOI: 10.1007/s10555-024-10197-4.

Viral cis-regulatory elements as sensors of cellular states and environmental cues.

Rottenberg J, Taslim T, Soto-Ugaldi L, Martinez-Cuesta L, Martinez-Calejman C, Fuxman Bass J Trends Genet. 2024; 40(9):772-783.

PMID: 38821843 PMC: 11387143. DOI: 10.1016/j.tig.2024.05.004.

Carcinogenic mechanisms of virus-associated lymphoma.

Zhang Y, Guo W, Zhan Z, Bai O Front Immunol. 2024; 15:1361009.

PMID: 38482011 PMC: 10932979. DOI: 10.3389/fimmu.2024.1361009.

Epstein-Barr virus: the mastermind of immune chaos.

Silva J, de Castro Alves C, Pontes G Front Immunol. 2024; 15:1297994.

PMID: 38384471 PMC: 10879370. DOI: 10.3389/fimmu.2024.1297994.

Functional diversity: update of the posttranslational modification of Epstein-Barr virus coding proteins.

Sun Y, Liu W, Luo B Cell Mol Life Sci. 2022; 79(12):590.

PMID: 36376593 PMC: 11802978. DOI: 10.1007/s00018-022-04561-2.

References

Cohen J, Wang F, MANNICK J, Kieff E . Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci U S A. 1989; 86(23):9558-62. PMC: 298536. DOI: 10.1073/pnas.86.23.9558. View

Gahn T, SCHILDKRAUT C . The Epstein-Barr virus origin of plasmid replication, oriP, contains both the initiation and termination sites of DNA replication. Cell. 1989; 58(3):527-35. DOI: 10.1016/0092-8674(89)90433-9. View

Zimber-Strobl U, Suentzenich K, Laux G, Eick D, Cordier M, Calender A . Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene. J Virol. 1991; 65(1):415-23. PMC: 240532. DOI: 10.1128/JVI.65.1.415-423.1991. View

Alfieri C, Birkenbach M, Kieff E . Early events in Epstein-Barr virus infection of human B lymphocytes. Virology. 1991; 181(2):595-608. DOI: 10.1016/0042-6822(91)90893-g. View

Woisetschlaeger M, Jin X, Yandava C, Furmanski L, Strominger J, Speck S . Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection. Proc Natl Acad Sci U S A. 1991; 88(9):3942-6. PMC: 51569. DOI: 10.1073/pnas.88.9.3942. View

Tsang S, Wang F, Izumi K, Kieff E . Delineation of the cis-acting element mediating EBNA-2 transactivation of latent infection membrane protein expression. J Virol. 1991; 65(12):6765-71. PMC: 250762. DOI: 10.1128/JVI.65.12.6765-6771.1991. View

Middleton T, Gahn T, Martin J, Sugden B . Immortalizing genes of Epstein-Barr virus. Adv Virus Res. 1991; 40:19-55. DOI: 10.1016/s0065-3527(08)60276-6. View

Fennewald S, van Santen V, Kieff E . Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol. 1984; 51(2):411-9. PMC: 254453. DOI: 10.1128/JVI.51.2.411-419.1984. View

Baer R, Bankier A, Biggin M, Deininger P, Farrell P, Gibson T . DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984; 310(5974):207-11. DOI: 10.1038/310207a0. View

10.

Rawlins D, Milman G, Hayward S, Hayward G . Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985; 42(3):859-68. DOI: 10.1016/0092-8674(85)90282-x. View

11.

Reisman D, Yates J, Sugden B . A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985; 5(8):1822-32. PMC: 366897. DOI: 10.1128/mcb.5.8.1822-1832.1985. View

12.

Reisman D, Sugden B . trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol. 1986; 6(11):3838-46. PMC: 367146. DOI: 10.1128/mcb.6.11.3838-3846.1986. View

13.

Hurley E, Thorley-Lawson D . B cell activation and the establishment of Epstein-Barr virus latency. J Exp Med. 1988; 168(6):2059-75. PMC: 2189139. DOI: 10.1084/jem.168.6.2059. View

14.

Rooney C, Howe J, Speck S, Miller G . Influence of Burkitt's lymphoma and primary B cells on latent gene expression by the nonimmortalizing P3J-HR-1 strain of Epstein-Barr virus. J Virol. 1989; 63(4):1531-9. PMC: 248385. DOI: 10.1128/JVI.63.4.1531-1539.1989. View

15.

Sugden B, Warren N . A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J Virol. 1989; 63(6):2644-9. PMC: 250748. DOI: 10.1128/JVI.63.6.2644-2649.1989. View

16.

Rooney C, Brimmell M, Buschle M, Allan G, Farrell P, Kolman J . Host cell and EBNA-2 regulation of Epstein-Barr virus latent-cycle promoter activity in B lymphocytes. J Virol. 1992; 66(1):496-504. PMC: 238310. DOI: 10.1128/JVI.66.1.496-504.1992. View

17.

Gahn T, Sugden B . Marked, transient inhibition of expression of the Epstein-Barr virus latent membrane protein gene in Burkitt's lymphoma cell lines by electroporation. J Virol. 1993; 67(11):6379-86. PMC: 238072. DOI: 10.1128/JVI.67.11.6379-6386.1993. View

18.

Ling P, Rawlins D, Hayward S . The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a cellular enhancer-binding protein. Proc Natl Acad Sci U S A. 1993; 90(20):9237-41. PMC: 47542. DOI: 10.1073/pnas.90.20.9237. View

19.

Pallesen G, Hamilton-Dutoit S, Zhou X . The association of Epstein-Barr virus (EBV) with T cell lymphoproliferations and Hodgkin's disease: two new developments in the EBV field. Adv Cancer Res. 1993; 62:179-239. DOI: 10.1016/s0065-230x(08)60319-x. View

20.

Henkel T, Ling P, Hayward S, Peterson M . Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. Science. 1994; 265(5168):92-5. DOI: 10.1126/science.8016657. View