background:
Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBSLVpositive cell lines. BRLF1 is a transcriptional activator that binds directly to a GSLCrich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
BRLF1是EBV的立即早期基因。作为一种反式激活因子，它可以调节EBV早期／晚期基因的表达．并且还可能参与裂解期病毒基因组的复制。它的表达与EBV潜伏周期向裂解周期的转换密切相关。BRLF1的蛋因白产物Rta包含CTL识别的表位，可能在病毒裂解周期的早期成为免疫系统的作用位点。对它研究还可能为某些EBV相关肿瘤的筛查和治疗提供线索。
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