Interferon regulatory factor (IRF)-2 activates the HPV-16 E6-E7 promoter in keratinocytes
Interferon regulatory factor (IRF)-2 activates the HPV-16 E6-E7 promoter in keratinocytes
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DOI：
10.1016/j.virol.2009.12.025
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发表时间：
2010-04-10
期刊：
影响因子：
3.7
通讯作者：
Turek, Lubomir P.
中科院分区：
文献类型：
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作者：
Lace, Michael J.;Anson, James R.;Turek, Lubomir P.
干扰素调节因子（IRFs）是基因表达、细胞生长和免疫应答的重要介质。我们之前证明干扰素（IFN）在几种粘膜hpv中诱导早期病毒转录和复制需要IRF-1与保守的干扰素反应元件（IRE）结合。在这里，我们发现IRF-2蛋白作为HPV-16主要早期启动子P97的基线反激活子。IRF敲除细胞的共转染证实，基本的HPV-16启动子活性由IRF-1和IRF-2复合物支持，IRF-1和IRF-2复合物以剂量依赖的方式与启动子-近端IRE相互作用。此外，HPV-16 E7表达下调IRF-2启动子，从而通过负反馈机制将IRF-2水平与病毒转化基因表达联系起来。综上所述，这些观察结果揭示了在HPV持久性的建立和维持过程中利用多种信号转导途径的复杂病毒策略。Elsevier Inc.出版。
Interferon regulatory factors (IRFs) are critical mediators of gene expression, cell growth and immune responses. We previously demonstrated that interferon (IFN) induction of early viral transcription and replication in several mucosal HPVs requires IRF-1 binding to a conserved interferon response element (IRE). Here we show that the IRF-2 protein served as a baseline transactivator of the HPV-16 major early promoter, P97. Cotransfections in IRF knockout cells confirmed that basal HPV-16 promoter activity was supported by both IRF-1 and IRF-2 complexes interacting with the promoter-proximal IRE in a dose-dependent manner. Furthermore, HPV-16 E7 expression downregulates the IRF-2 promoter, thus linking IRF-2 levels to viral transforming gene expression through a negative feedback mechanism. Taken together, these observations reveal a complex viral strategy utilizing multiple signal transduction pathways during the establishment and maintenance of HPV persistence. Published by Elsevier Inc.