Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1992 May; 66(5): 2689–2697.
PMCID: PMC241023

Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts.


Epstein-Barr virus (EBV) genome-positive nasopharyngeal carcinomas (NPCs) regularly express the virus-coded nuclear antigen EBNA1, but not other EBNAs, and a subset of tumors also appear to be latent membrane protein LMP1 positive; the status of NPCs with respect to a second virus-coded latent membrane protein LMP2 is unknown. In the present work the EBV-NPC cell interaction has been analyzed at the RNA level with reverse transcription and polymerase chain reaction-based amplification to detect specific latent viral mRNAs. All four transplantable NPC cell lines studied and 17 of 18 fresh snap-frozen NPC biopsy specimens expressed an EBNA1 mRNA with a BamHI Q/U/K splice structure exactly like that recently identified in group I Burkitt's lymphoma (BL) cell lines and shown to be driven from a novel viral promoter, Fp. The BamHI Y3/U/K-spliced EBNA1 mRNA characteristic of virus-transformed B-lymphoblastoid cell lines (LCLs) was never found in NPCs. These same NPC biopsy specimens were then analyzed for evidence of the various LMP transcripts which are constitutively expressed in LCLs but down-regulated in BL cells. While only 3 of 18 tumors gave a clear LMP1 mRNA-specific signal after first-round amplification with either of two sets of polymerase chain reaction primers, the majority proved to be LMP1 mRNA positive after second-round amplification with nested primers. A rather similar pattern of results was obtained with respect to LMP2B mRNA expression, such transcripts being detectable only in a subset of tumors, and then at apparently low levels. In contrast, clear evidence of LMP2A mRNA expression was obtained in 17 of 17 fresh biopsies. The predominant form of EBV infection in NPCs, with coexpression of EBNA1 and LMP mRNAs, is therefore quite distinct from that seen in BL cells (in which EBNA1 is the only expressed mRNA) and in LCL cells (in which all six EBNA and three LMP transcripts are present). This third form of EBV latency may not be restricted to NPC but may have more general relevance in the context of EBV infection in vivo.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Abbot SD, Rowe M, Cadwallader K, Ricksten A, Gordon J, Wang F, Rymo L, Rickinson AB. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. J Virol. 1990 May;64(5):2126–2134. [PMC free article] [PubMed]
  • Alfieri C, Birkenbach M, Kieff E. Early events in Epstein-Barr virus infection of human B lymphocytes. Virology. 1991 Apr;181(2):595–608. [PubMed]
  • Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Séguin C, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. [PubMed]
  • Busson P, Ganem G, Flores P, Mugneret F, Clausse B, Caillou B, Braham K, Wakasugi H, Lipinski M, Tursz T. Establishment and characterization of three transplantable EBV-containing nasopharyngeal carcinomas. Int J Cancer. 1988 Oct 15;42(4):599–606. [PubMed]
  • Dawson CW, Rickinson AB, Young LS. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990 Apr 19;344(6268):777–780. [PubMed]
  • Fåhraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G, Falk K, Nilsson E, Yadav M, Busson P, et al. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 1988 Sep 15;42(3):329–338. [PubMed]
  • Fåhraeus R, Jansson A, Ricksten A, Sjöblom A, Rymo L. Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7390–7394. [PMC free article] [PubMed]
  • Fåhraeus R, Rymo L, Rhim JS, Klein G. Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature. 1990 May 31;345(6274):447–449. [PubMed]
  • Frech B, Zimber-Strobl U, Suentzenich KO, Pavlish O, Lenoir GM, Bornkamm GW, Mueller-Lantzsch N. Identification of Epstein-Barr virus terminal protein 1 (TP1) in extracts of four lymphoid cell lines, expression in insect cells, and detection of antibodies in human sera. J Virol. 1990 Jun;64(6):2759–2767. [PMC free article] [PubMed]
  • Gilligan K, Sato H, Rajadurai P, Busson P, Young L, Rickinson A, Tursz T, Raab-Traub N. Novel transcription from the Epstein-Barr virus terminal EcoRI fragment, DIJhet, in a nasopharyngeal carcinoma. J Virol. 1990 Oct;64(10):4948–4956. [PMC free article] [PubMed]
  • Gregory CD, Rowe M, Rickinson AB. Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt's lymphoma cell line. J Gen Virol. 1990 Jul;71(Pt 7):1481–1495. [PubMed]
  • Hennessy K, Kieff E. One of two Epstein-Barr virus nuclear antigens contains a glycine-alanine copolymer domain. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5665–5669. [PMC free article] [PubMed]
  • Hitt MM, Allday MJ, Hara T, Karran L, Jones MD, Busson P, Tursz T, Ernberg I, Griffin BE. EBV gene expression in an NPC-related tumour. EMBO J. 1989 Sep;8(9):2639–2651. [PMC free article] [PubMed]
  • Hu LF, Zabarovsky ER, Chen F, Cao SL, Ernberg I, Klein G, Winberg G. Isolation and sequencing of the Epstein-Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma. J Gen Virol. 1991 Oct;72(Pt 10):2399–2409. [PubMed]
  • Hudson GS, Farrell PJ, Barrell BG. Two related but differentially expressed potential membrane proteins encoded by the EcoRI Dhet region of Epstein-Barr virus B95-8. J Virol. 1985 Feb;53(2):528–535. [PMC free article] [PubMed]
  • Johnson MA, Blomfield PI, Bevan IS, Woodman CB, Young LS. Analysis of human papillomavirus type 16 E6-E7 transcription in cervical carcinomas and normal cervical epithelium using the polymerase chain reaction. J Gen Virol. 1990 Jul;71(Pt 7):1473–1479. [PubMed]
  • Laux G, Economou A, Farrell PJ. The terminal protein gene 2 of Epstein-Barr virus is transcribed from a bidirectional latent promoter region. J Gen Virol. 1989 Nov;70(Pt 11):3079–3084. [PubMed]
  • Laux G, Perricaudet M, Farrell PJ. 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):769–774. [PMC free article] [PubMed]
  • Longnecker R, Kieff E. A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. J Virol. 1990 May;64(5):2319–2326. [PMC free article] [PubMed]
  • Raab-Traub N, Hood R, Yang CS, Henry B, 2nd, Pagano JS. Epstein-Barr virus transcription in nasopharyngeal carcinoma. J Virol. 1983 Dec;48(3):580–590. [PMC free article] [PubMed]
  • 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 Nov;6(11):3838–3846. [PMC free article] [PubMed]
  • Rogers RP, Woisetschlaeger M, Speck SH. Alternative splicing dictates translational start in Epstein-Barr virus transcripts. EMBO J. 1990 Jul;9(7):2273–2277. [PMC free article] [PubMed]
  • Rowe M, Lear AL, Croom-Carter D, Davies AH, Rickinson AB. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992 Jan;66(1):122–131. [PMC free article] [PubMed]
  • Rowe M, Rowe DT, Gregory CD, Young LS, Farrell PJ, Rupani H, Rickinson AB. 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):2743–2751. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sample J, Brooks L, Sample C, Young L, Rowe M, Gregory C, Rickinson A, Kieff E. Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6343–6347. [PMC free article] [PubMed]
  • Sample J, Liebowitz D, Kieff E. Two related Epstein-Barr virus membrane proteins are encoded by separate genes. J Virol. 1989 Feb;63(2):933–937. [PMC free article] [PubMed]
  • Smith PR, Griffin BE. Differential expression of Epstein Barr viral transcripts for two proteins (TP1 and LMP) in lymphocyte and epithelial cells. Nucleic Acids Res. 1991 May 11;19(9):2435–2440. [PMC free article] [PubMed]
  • Summers WP, Grogan EA, Shedd D, Robert M, Liu CR, Miller G. Stable expression in mouse cells of nuclear neoantigen after transfer of a 3.4-megadalton cloned fragment of Epstein-Barr virus DNA. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5688–5692. [PMC free article] [PubMed]
  • Tugwood JD, Lau WH, O SK, Tsao SY, Martin WM, Shiu W, Desgranges C, Jones PH, Arrand JR. Epstein-Barr virus-specific transcription in normal and malignant nasopharyngeal biopsies and in lymphocytes from healthy donors and infectious mononucleosis patients. J Gen Virol. 1987 Apr;68(Pt 4):1081–1091. [PubMed]
  • Wang D, Liebowitz D, Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985 Dec;43(3 Pt 2):831–840. [PubMed]
  • Wang F, Tsang SF, Kurilla MG, Cohen JI, Kieff E. Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. J Virol. 1990 Jul;64(7):3407–3416. [PMC free article] [PubMed]
  • Wilson JB, Weinberg W, Johnson R, Yuspa S, Levine AJ. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell. 1990 Jun 29;61(7):1315–1327. [PubMed]
  • Yates J, Warren N, Reisman D, Sugden B. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806–3810. [PMC free article] [PubMed]
  • Yates JL, Warren N, Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature. 313(6005):812–815. [PubMed]
  • Young LS, Dawson CW, Clark D, Rupani H, Busson P, Tursz T, Johnson A, Rickinson AB. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988 May;69(Pt 5):1051–1065. [PubMed]
  • Zimber-Strobl U, Suentzenich KO, Laux G, Eick D, Cordier M, Calender A, Billaud M, Lenoir GM, Bornkamm GW. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene. J Virol. 1991 Jan;65(1):415–423. [PMC free article] [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...