1887

Abstract

Epstein–Barr virus (EBV) HI-A rightward transcripts (BARTs; also designated complementary strand transcripts or CSTs) have been demonstrated to contain several splicing forms in EBV-infected cells. To date, however, little is known about the actual full-length splicing form and its functions. In the present study, we proved that six forms of BARTs were present in EBV-positive cell lines and various tissue specimens with different EBV infection patterns. Of the BART-encoded genes, mRNA of four major splicing forms, including BARF0, RPMS1, RPMS1A and A73, were expressed in all EBV-infected cells. On the other hand, mRNA of two minor splicing forms, RK-BARF0 and RB3, was rarely detected, or if at all, at very low expression levels. Both RPMS1A and RPMS1 mRNA was transcribed at higher levels in EBV-infected cells. In particular, RPMS1 mRNA was expressed abundantly in epithelial carcinoma cells, including gastric carcinoma and nasopharyngeal carcinoma, in association with a lytic infection signal, BZLF1 mRNA. The four major splicing forms were expressed much less in B-cell lines with an integrated EBV genome than in those with episomal EBV genomes. These data indicate that at least six splicing forms can be expressed by EBV-infected cells or tissues, although the expression patterns or levels differ for different infection states such as lytic and latent infections.

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2012-10-01
2024-12-05
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References

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C. other authors 1984; DNA sequence and expression of the B95-8 Epstein–Barr virus genome. Nature 310:207–211 [View Article][PubMed]
    [Google Scholar]
  2. Brooks L. A., Lear A. L., Young L. S., Rickinson A. B. 1993; Transcripts from the Epstein-Barr virus BamHI A fragment are detectable in all three forms of virus latency. J Virol 67:3182–3190[PubMed]
    [Google Scholar]
  3. Cai X., Schäfer A., Lu S., Bilello J. P., Desrosiers R. C., Edwards R., Raab-Traub N., Cullen B. R. 2006; Epstein–Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog 2:e23 [View Article][PubMed]
    [Google Scholar]
  4. Chen H. L., Lung M. M., Sham J. S., Choy D. T., Griffin B. E., Ng M. H. 1992; Transcription of BamHI-A region of the EBV genome in NPC tissues and B cells. Virology 191:193–201 [View Article][PubMed]
    [Google Scholar]
  5. Chen H., Smith P., Ambinder R. F., Hayward S. D. 1999; Expression of Epstein-Barr virus BamHI-A rightward transcripts in latently infected B cells from peripheral blood. Blood 93:3026–3032[PubMed]
    [Google Scholar]
  6. Chen H., Huang J., Wu F. Y., Liao G., Hutt-Fletcher L., Hayward S. D. 2005; Regulation of expression of the Epstein-Barr virus BamHI-A rightward transcripts. J Virol 79:1724–1733 [View Article][PubMed]
    [Google Scholar]
  7. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillie J., Sergeant A. 1986; Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J 5:3243–3249[PubMed]
    [Google Scholar]
  8. Chien Y. C., Chen J. Y., Liu M. Y., Yang H. I., Hsu M. M., Chen C. J., Yang C. S. 2001; Serologic markers of Epstein–Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 345:1877–1882 [View Article][PubMed]
    [Google Scholar]
  9. Daibata M., Taguchi T., Nemoto Y., Saito T., Machida H., Imai S., Miyoshi I., Taguchi H. 2002; Epstein–Barr virus (EBV)-positive pyothorax-associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2-positive PAL B-cell line. Br J Haematol 117:546–557 [View Article][PubMed]
    [Google Scholar]
  10. de Jesus O., Smith P. R., Spender L. C., Elgueta Karstegl C., Niller H. H., Huang D., Farrell P. J. 2003; Updated Epstein–Barr virus (EBV) DNA sequence and analysis of a promoter for the BART (CST, BARF0) RNAs of EBV. J Gen Virol 84:1443–1450 [View Article][PubMed]
    [Google Scholar]
  11. Edwards R. H., Marquitz A. R., Raab-Traub N. 2008; Epstein-Barr virus BART microRNAs are produced from a large intron prior to splicing. J Virol 82:9094–9106 [View Article][PubMed]
    [Google Scholar]
  12. Fries K. L., Sculley T. B., Webster-Cyriaque J., Rajadurai P., Sadler R. H., Raab-Traub N. 1997; Identification of a novel protein encoded by the BamHI A region of the Epstein-Barr virus. J Virol 71:2765–2771[PubMed]
    [Google Scholar]
  13. Gilligan K. J., Rajadurai P., Lin J. C., Busson P., Abdel-Hamid M., Prasad U., Tursz T., Raab-Traub N. 1991; Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo. J Virol 65:6252–6259[PubMed]
    [Google Scholar]
  14. Hitt M. M., Allday M. J., Hara T., Karran L., Jones M. D., Busson P., Tursz T., Ernberg I., Griffin B. E. 1989; EBV gene expression in an NPC-related tumour. EMBO J 8:2639–2651[PubMed]
    [Google Scholar]
  15. Hoshikawa Y., Satoh Y., Murakami M., Maeta M., Kaibara N., Ito H., Kurata T., Sairenji T. 2002; Evidence of lytic infection of Epstein-Barr virus (EBV) in EBV-positive gastric carcinoma. J Med Virol 66:351–359 [View Article][PubMed]
    [Google Scholar]
  16. Imai S., Nishikawa J., Takada K. 1998; Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of diverse human epithelial cells. J Virol 72:4371–4378[PubMed]
    [Google Scholar]
  17. Karran L., Gao Y., Smith P. R., Griffin B. E. 1992; Expression of a family of complementary-strand transcripts in Epstein-Barr virus-infected cells. Proc Natl Acad Sci U S A 89:8058–8062 [View Article][PubMed]
    [Google Scholar]
  18. Kienzle N., Sculley T. B., Poulsen L., Buck M., Cross S., Raab-Traub N., Khanna R. 1998; Identification of a cytotoxic T-lymphocyte response to the novel BARF0 protein of Epstein-Barr virus: a critical role for antigen expression. J Virol 72:6614–6620[PubMed]
    [Google Scholar]
  19. Kienzle N., Sculley T. B., Greco S., Khanna R. 1999; Cutting edge: silencing virus-specific cytotoxic T cell-mediated immune recognition by differential splicing: a novel implication of RNA processing for antigen presentation. J Immunol 162:6963–6966[PubMed]
    [Google Scholar]
  20. Lawrence J. B., Villnave C. A., Singer R. H. 1988; Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell 52:51–61 [View Article][PubMed]
    [Google Scholar]
  21. Lear A. L., Rowe M., Kurilla M. G., Lee S., Henderson S., Kieff E., Rickinson A. B. 1992; The Epstein-Barr virus (EBV) nuclear antigen 1 BamHI F promoter is activated on entry of EBV-transformed B cells into the lytic cycle. J Virol 66:7461–7468[PubMed]
    [Google Scholar]
  22. Ooka T., De Turenne M., De The G., Daillie J. 1984; Epstein-Barr virus-specific DNase activity in nonproducer Raji cells after treatment with 12-o-tetradecanoylphorbol-13-acetate and sodium butyrate. J Virol 49:626–628[PubMed]
    [Google Scholar]
  23. Parker B. D., Bankier A., Satchwell S., Barrell B., Farrell P. J. 1990; Sequence and transcription of Raji Epstein-Barr virus DNA spanning the B95-8 deletion region. Virology 179:339–346 [View Article][PubMed]
    [Google Scholar]
  24. Pfeffer S., Zavolan M., Grässer F. A., Chien M., Russo J. J., Ju J., John B., Enright A. J., Marks D. other authors 2004; Identification of virus-encoded microRNAs. Science 304:734–736 [View Article][PubMed]
    [Google Scholar]
  25. Rickinson A. B., Kieff E. 2001; Epstein-Barr Virus. In Fields Virology pp. 2575–2627 Philadelphia, PA: Lippincott-Raven;
    [Google Scholar]
  26. Sadler R. H., Raab-Traub N. 1995; Structural analyses of the Epstein-Barr virus BamHI A transcripts. J Virol 69:1132–1141[PubMed]
    [Google Scholar]
  27. Smith P. R. 2001; Epstein–Barr virus complementary strand transcripts (CSTs/BARTs) and cancer. Semin Cancer Biol 11:469–476 [View Article][PubMed]
    [Google Scholar]
  28. Smith P. R., Gao Y., Karran L., Jones M. D., Snudden D., Griffin B. E. 1993; Complex nature of the major viral polyadenylated transcripts in Epstein-Barr virus-associated tumors. J Virol 67:3217–3225[PubMed]
    [Google Scholar]
  29. Smith P. R., de Jesus O., Turner D., Hollyoake M., Karstegl C. E., Griffin B. E., Karran L., Wang Y., Hayward S. D., Farrell P. J. 2000; Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus. J Virol 74:3082–3092 [View Article][PubMed]
    [Google Scholar]
  30. Speck S. H., Chatila T., Flemington E. 1997; Reactivation of Epstein–Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol 5:399–405 [View Article][PubMed]
    [Google Scholar]
  31. Takakuwa T., Luo W. J., Ham M. F., Mizuki M., Iuchi K., Aozasa K. 2003; Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is strongly associated with Epstein-Barr virus infection. Cancer Sci 94:858–863 [View Article][PubMed]
    [Google Scholar]
  32. Yamamoto T., Tsuji K., Suzuki D., Morizane S., Iwatsuki K. 2007; A novel, noninvasive diagnostic probe for hydroa vacciniforme and related disorders: detection of latency-associated Epstein-Barr virus transcripts in the crusts. J Microbiol Methods 68:403–407 [View Article][PubMed]
    [Google Scholar]
  33. Zhang C. X., Ooka T. 1995; Expression of the complementary-strand transcripts from BamHI-A region of the Epstein-Barr virus genome in various induced virus-carrying B cell lines. Virology 208:180–188 [View Article][PubMed]
    [Google Scholar]
  34. Zhang J., Chen H., Weinmaster G., Hayward S. D. 2001; Epstein-Barr virus BamHI-A rightward transcript-encoded RPMS protein interacts with the CBF1-associated corepressor CIR to negatively regulate the activity of EBNA2 and NotchIC. J Virol 75:2946–2956 [View Article][PubMed]
    [Google Scholar]
  35. zur Hausen H., O’Neill F. J., Freese U. K., Hecker E. 1978; Persisting oncogenic herpesvirus induced by the tumour promotor TPA. Nature 272:373–375 [View Article][PubMed]
    [Google Scholar]
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