the b-cell specific transcription factor, oct-2, promotes epstein-barr virus latency by inhibiting the viral immediate-early protein, bzlf1b细胞特定的转录因子,oct-2,促进eb病毒潜伏期通过抑制病毒即早期蛋白质,bzlf1.pdf
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The B-Cell Specific Transcription Factor, Oct-2, Promotes
Epstein-Barr Virus Latency by Inhibiting the Viral
Immediate-Early Protein, BZLF1
1,2 1 1,3
Amanda R. Robinson , Swee Sen Kwek , Shannon C. Kenney *
1 Department of Oncology, McArdle Laboratory for Cancer Research , University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of
America, 2 Department of Cellular and Molecular Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America,
3 Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
Abstract
The Epstein-Barr virus (EBV) latent-lytic switch is mediated by the BZLF1 immediate-early protein. EBV is normally latent in
memory B cells, but cellular factors which promote viral latency specifically in B cells have not been identified. In this report,
we demonstrate that the B-cell specific transcription factor, Oct-2, inhibits the function of the viral immediate-early protein,
BZLF1, and prevents lytic viral reactivation. Co-transfected Oct-2 reduces the ability of BZLF1 to activate lytic gene
expression in two different latently infected nasopharyngeal carcinoma cell lines. Furthermore, Oct-2 inhibits BZLF1
activation of lytic EBV promoters in reporter gene assays, and attenuates BZLF1 binding to lytic viral promoters in vivo. Oct-2
interacts directly with BZLF1, and this interaction requires the DNA-binding/dimerization domain of BZLF1 and the POU
domain of Oct-2. An Oct-2 mutant (D262–302) deficient for interaction with BZLF1 is unable to inhibit BZLF1-mediated lytic
reactivation. However, an Oct-2 mutant defective for DNA-
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