The B-cell specific transcription factor,Oct-2,promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein,BZLF1

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 (δ262-302) deficient for interaction with bzlf1 is unable to inhibit bzlf1-mediated lytic reactivation. however,an oct-2 mutant defective for dna-binding (q221a) retains the ability to inhibit bzlf1 transcriptional effects and dna-binding. importantly,shrna-mediated knockdown of endogenous oct-2 expression in several ebv-positive burkitt lymphoma and lymphoblastoid cell lines increases the level of lytic ebv gene expression,while decreasing ebna1 expression. moreover,treatments which induce ebv lytic reactivation,such as anti-igg cross-linking and chemical inducers,also decrease the level of oct-2 protein expression at the transcriptional level. we conclude that oct-2 potentiates establishment of ebv latency in b cells. © 2012 robinson et al.