J Gen Virol
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Published online ahead of print on 24 June 2009 as doi:10.1099/vir.0.012831-0
Journal of General Virology 2009;90:2331.

A more recent version of this article appeared on October 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.012831-0
© 2009 Society for General Microbiology

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Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation

Koichi Ricardo Katsumura, Seiji Maruo, Yi Wu, Teru Kanda and Kenzo Takada1

Institute for Genetic Medicine, Hokkaido University

1 E-mail: kentaka{at}igm.hokudai.ac.jp

The Epstein-Barr virus (EBV) immediate-early transactivator BZLF1 plays a key role in switching EBV infection from latent to lytic form by stimulating the expression cascade of lytic genes; it also regulates the expression of several cellular genes. Recently, we reported that BZLF1 is expressed in primary human B cells early after EBV infection. To investigate whether this BZLF1 expression early after infection plays a role in the EBV-induced growth transformation of primary B cells, we generated BZLF1-knockout EBV and quantitatively evaluated its transforming ability compared to that of wild-type EBV. We found that the 50% transforming dose of BZLF1-knockout EBV was quite similar to that of wild-type EBV. Established lymphoblastoid cell lines (LCLs) harboring BZLF1-knockout EBV were indistinguishable from LCLs harboring wild-type EBV in their pattern of latent gene expression and in their growth in vitro. Furthermore, the copy numbers of EBV episomes were very similar in the LCLs harboring BZLF1-knockout EBV and the LCLs harboring wild-type EBV. These data indicate that disrupting BZLF1 expression in the context of the EBV genome, and the resultant inability to enter lytic replication, has little impact on the growth of LCLs and the steady-state copy number of EBV episomes in established LCLs.

Received 20 April 2009; accepted 19 June 2009.


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