Advertisement

Virus Genes

, Volume 55, Issue 6, pp 779–785 | Cite as

BZLF1 transcript variants in Epstein–Barr virus-positive epithelial cell lines

  • Jason Needham
  • Amy L. AdamsonEmail author
Original Paper
  • 78 Downloads

Abstract

Epstein–Barr virus (EBV) is a widely prevalent pathogen currently infecting over 90% of the human population and is associated with various lymphomas and carcinomas. Lytic replication of EBV is regulated by the expression of the immediate-early genes BZLF1 and BRLF1. In B lymphocytes, BZLF1 transcripts have been shown to be processed to a fully spliced form, as well as zDelta, a spliced variant containing only the first and third exons. While splice variants have been reported in nasopharyngeal carcinoma biopsies, alternative splicing of BZLF1 in EBV-positive epithelial cell lines has not yet been characterized. In this study, we identified the consistent expression of three distinct BZLF1 transcripts in the EBV-positive epithelial cell lines D98/HR1, AGS-BDneo, and AGS-BX1. These BZLF1 transcripts consisted of not only the normally spliced variant but also a completely unspliced and a spliced variant containing exons one and three only. In contrast, we detected only the normally spliced version of the BZLF1 transcript in B-cell lines (B95-8, IM-9, Raji and Daudi). Previous work has also demonstrated that inhibition of the mTOR pathway, via rapamycin, altered total levels of BZLF1 transcripts. We examined the production of specific transcript variants under rapamycin treatment and found that rapamycin alters the production of transcripts in a cell-type, as well as transcripts in variant-type, manners. The expression of these transcript variants may play a role in modulating the replication cycle of EBV within epithelial cells.

Keywords

Epstein–Barr virus BZLF1 Transcript mTOR Splicing 

Notes

Acknowledgements

We would like to thank Ibeabuchi Iloghalu for assistance with this project.

Author contributions

JN conceived of experiments; JN and AA carried out experiments; AA and JN wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

There were no human participants in this study.

Research involving human and animal participants

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Rickinson AB, Kieff E (2007) Epstein–Barr virus. In: Howley PMN, Knipe DM (eds) Field’s Virology. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  2. 2.
    Murata T, Sato Y, Kimura H (2014) Modes of infection and oncogenesis by the Epstein–Barr virus. Rev Med Virol 24:242–253.  https://doi.org/10.1002/rmv.1786 CrossRefPubMedGoogle Scholar
  3. 3.
    Kieff E, Rickinson AB (2007) Epstein–Barr virus and its replication. In: Knipe DM, Howley PM (eds) Field’s Virology. Lippincott Williams & Wilkins, Philadelphia, pp 2603–2654Google Scholar
  4. 4.
    Flemington E, Speck SH (1990) Autoregulation of Epstein–Barr virus putative lytic switch gene BZLF1. J Virol 64:1227–1232PubMedPubMedCentralGoogle Scholar
  5. 5.
    Ajiro M, Zheng Z-M (2014) Oncogenes and RNA splicing of human tumor viruses. Emerg Microbes Infect 3:e63.  https://doi.org/10.1038/emi.2014.62 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lau R, Packham G, Farrell PJ (1992) Differential splicing of Epstein–Barr virus immediate-early RNA. J Virol 66:6233–6236PubMedPubMedCentralGoogle Scholar
  7. 7.
    Furnari FB, Zacny V, Quinlivan EB et al (1994) RAZ, an Epstein–Barr virus transdominant repressor that modulates the viral reactivation mechanism. J Virol 68:1827–1836PubMedPubMedCentralGoogle Scholar
  8. 8.
    Cochet C, Martel-Renoir D, Grunewald V et al (1993) Expression of the Epstein–Barr virus immediate early gene, BZLF1, in nasopharyngeal carcinoma tumor cells. Virology 197:358–365.  https://doi.org/10.1006/viro.1993.1597 CrossRefPubMedGoogle Scholar
  9. 9.
    Kenney SC, Mertz JE (2014) Regulation of the latent-lytic switch in Epstein–Barr virus. Semin Cancer Biol 26:60–68.  https://doi.org/10.1016/j.semcancer.2014.01.002 CrossRefPubMedGoogle Scholar
  10. 10.
    Cunningham JT, Rodgers JT, Arlow DH et al (2007) mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 450:736–740.  https://doi.org/10.1038/nature06322 CrossRefPubMedGoogle Scholar
  11. 11.
    Laplante M, Sabatini DM (2013) Regulation of mTORC1 and its impact on gene expression at a glance. J Cell Sci 126:1713–1719.  https://doi.org/10.1242/jcs.125773 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Adamson AL, Le BT, Siedenburg BD (2014) Inhibition of mTORC1 inhibits lytic replication of Epstein–Barr virus in a cell-type specific manner. Virol J 11:110.  https://doi.org/10.1186/1743-422X-11-110 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Arad U (1998) Modified Hirt procedure for rapid purification of extrachromosomal DNA from mammalian cells. Biotechniques 24:760–762.  https://doi.org/10.2144/98245bm14 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of North Carolina at GreensboroGreensboroUSA

Personalised recommendations