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Journal of Virology, October 2002, p. 10290-10298, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10290-10298.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Signal Transduction and Transcription Factor Modification during Reactivation of Epstein-Barr Virus from Latency

Helen Bryant1 and Paul J. Farrell1,2*

Ludwig Institute for Cancer Research,1 Virology and Cell Biology Section, Imperial College Faculty of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom2

Received 8 April 2002/ Accepted 12 July 2002

Reactivation of Epstein-Barr virus (EBV) from latency involves activation of the Zp promoter of the EBV BZLF1 gene. This occurs rapidly and efficiently in response to cross-linking the B-cell receptor on Akata Burkitt's lymphoma cells. After optimizing conditions for induction, signal transduction responses to B-cell receptor cross-linking were observed within 10 min, well before any autoactivation effects of BZLF1 protein. The primary events in reactivation were shown to involve dephosphorylation of the myocyte enhancer factor 2D (MEF-2D) transcription factor via the cyclosporin A-sensitive, calcium-mediated signaling pathway. This and other signal transduction events were correlated with the quantitative promoter analysis reported in the accompanying paper (U. K. Binné, W. Amon, and P. J. Farrell, this issue). Dephosphorylation of MEF-2D is known to be associated with histone acetylase recruitment, correlating with the histone acetylation at Zp during reactivation that we reported previously (Jenkins et al., J. Virol. 74:710-720, 2000). Histone deacetylation in response to phosphorylated MEF-2D can be mediated by class I or class II histone deacetylases (HDACs); HDAC 7 was the most readily detected class II HDAC in Akata and Raji cells, suggesting that it may be involved in Zp repression during latency.


* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 20 7563 7703. Fax: 44 20 7724 8586. E-mail: p.farrell{at}ic.ac.uk.


Journal of Virology, October 2002, p. 10290-10298, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10290-10298.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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