Interferon regulatory factor 5 represses expression of the Epstein-Barr virus oncoprotein LMP1: Braking of the IRF7/LMP1 regulatory circuit
Interferon regulatory factor 5 represses expression of the Epstein-Barr virus oncoprotein LMP1: Braking of the IRF7/LMP1 regulatory circuit
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DOI：
10.1128/jvi.79.18.11671-11676.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Pagano, JS
中科院分区：
文献类型：
--
作者：
Ning, SB;Huye, LE;Pagano, JS
我们已经报道了干扰素调节因子7 （IRF7）和eb病毒（EBV）癌蛋白1 （LMP1）之间的正调控回路的证据（S. Ning, a . M. Hahn， J. S. Pagano， J.中国医学杂志，77:9359-9368,2003）。为了探索这一回路可能的制动机制，我们分析了几种表达不同水平LMP1和IRF7蛋白的II型ebv感染细胞系，从而便于研究LMP1的表达调控。内源性IRF7和LMP1水平直接相关。IRF7显性阴性突变体的瞬时表达降低了LMP1水平。内源性IRF5和IRF7蛋白在ebv阳性细胞中显示出物理关联。IRF5的瞬时表达以剂量依赖的方式降低了IRF7对LMP1启动子的激活。最后，在这些细胞中转染IRF5显性阴性构建体或IRF5小干扰RNA导致内源性LMP1水平升高。这些结果表明，IRF5可能通过与IRF7相互作用下调IRFTs诱导LMP1的表达，并提供了一种调节IRF7和LMP1之间调控回路的手段。
We have reported evidence for a positive regulatory circuit between interferon regulatory factor 7 (IRF7) and the Epstein-Barr virus (EBV) oncoprotein 1 (LMP1) (S. Ning, A. M. Hahn, and J. S. Pagano, J. Virol. 77:9359-9368,2003). To explore a possible braking mechanism for this circuit, several type II EBV-infected cell lines that express different levels of LMP1 and IRF7 proteins and therefore are convenient for studying modulation of expression of LMP1 were analyzed. Endogenous levels of IRF7 and LMP1 were directly correlated. Transient expression of an IRF7 dominant-negative mutant decreased LMP1 levels. Endogenous IRF5 and IRF7 proteins were shown to physically associate in EBV-positive cells. Transient expression of IRF5 decreased activation of the LMP1 promoter by IRF7 in a dose-dependent manner. Finally, transfection of either an IRF5 dominant-negative construct or IRF5 small interfering RNA in these cells resulted in increases in endogenous levels of LMP1. These results indicate that IRF5 can downregulate IRFTs induction of expression of LMP1 most likely by interacting with IRF7 and provide a means of modulating a regulatory circuit between IRF7 and LMP1.