Advanced SearchSearch Tips
Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 4,  2016, pp.226-231
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.4.260
 Title & Authors
Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth
Noh, Ka-Won; Park, Jihyun; Kang, Myung-Soo;
  PDF(new window)
Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt`s lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders.
Cell death;EBNA1;Epstein-Barr Virus;Knockout;TALEN;
 Cited by
Antiviral therapy of persistent viral infection using genome editing, Current Opinion in Virology, 2016, 20, 85  crossref(new windwow)
Parkin DM (2006) The global health burden of infectionassociated cancers in the year 2002. Int J Cancer 118, 3030-3044 crossref(new window)

Granato M, Feederle R, Farina A et al (2008) Deletion of Epstein-Barr virus BFLF2 leads to impaired viral DNA packaging and primary egress as well as to the production of defective viral particles. J Virol 82, 4042-4051 crossref(new window)

Adams A and Lindahl T (1975) Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. Proc Natl Acad Sci U S A 72, 1477-1481 crossref(new window)

Raynaud FI, Whittaker SR, Fischer PM et al (2005) In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202. Clin Cancer Res 11, 4875-4887 crossref(new window)

Henderson A, Ripley S, Heller M and Kieff E (1983) Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro. Proc Natl Acad Sci U S A 80, 1987-1991 crossref(new window)

Matsuo T, Heller M, Petti L, O'Shiro E and Kieff E (1984) Persistence of the entire Epstein-Barr virus genome integrated into human lymphocyte DNA. Science 226, 1322-1325 crossref(new window)

Sugden B, Marsh K and Yates J (1985) A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol 5, 410-413 crossref(new window)

Yates JL, Warren N and Sugden B (1985) Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313, 812-815 crossref(new window)

Kang MS, Lee EK, Soni V et al (2011) Roscovitine inhibits EBNA1 serine 393 phosphorylation, nuclear localization, transcription, and episome maintenance. J Virol 85, 2859-2868 crossref(new window)

Kang MS, Hung SC and Kieff E (2001) Epstein-Barr virus nuclear antigen 1 activates transcription from episomal but not integrated DNA and does not alter lymphocyte growth. Proc Natl Acad Sci U S A 98, 15233-15238 crossref(new window)

Nasimuzzaman M, Kuroda M, Dohno S et al (2005) Eradication of epstein-barr virus episome and associated inhibition of infected tumor cell growth by adenovirus vector-mediated transduction of dominant-negative EBNA1. Mol Ther 11, 578-590 crossref(new window)

Yin Q and Flemington EK (2006) siRNAs against the Epstein Barr virus latency replication factor, EBNA1, inhibit its function and growth of EBV-dependent tumor cells. Virology 346, 385-393 crossref(new window)

Miller JC, Tan S, Qiao G et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29, 143-148 crossref(new window)

Kim SY, Song KA, Kieff E and Kang MS (2012) Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization. Biochem Biophys Res Commun 424, 251-256 crossref(new window)

Lee EK, Kim SY, Noh KW et al (2014) Small molecule inhibition of Epstein-Barr virus nuclear antigen-1 DNA binding activity interferes with replication and persistence of the viral genome. Antiviral Res 104C, 73-83 crossref(new window)

Cohen JI, Mocarski ES, Raab-Traub N, Corey L and Nabel GJ (2013) The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 31 Suppl 2, B194-196 crossref(new window)

Kim Y, Kweon J, Kim A et al (2013) A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 31, 251-258 crossref(new window)

Sung YH, Baek IJ, Kim DH et al (2013) Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol 31, 23-24 crossref(new window)

Sung YH, Baek IJ, Seong JK, Kim JS and Lee HW (2012) Mouse genetics: catalogue and scissors. BMB Rep 45, 686-692 crossref(new window)

Molesworth SJ, Lake CM, Borza CM, Turk SM and Hutt-Fletcher LM (2000) Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells. J Virol 74, 6324-6332 crossref(new window)

Park J, Bae EK, Lee C et al (2014) Establishment and characterization of bortezomib-resistant U266 cell line: constitutive activation of NF-kappaB-mediated cell signals and/or alterations of ubiquitylation-related genes reduce bortezomib-induced apoptosis. BMB Rep 47, 274-279 crossref(new window)