Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity
Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity
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DOI：
10.1101/gad.12.13.2061
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发表时间：
1998-07-01
影响因子：
10.5
通讯作者：
Howley, PM
中科院分区：
文献类型：
--
作者：
Ronco, LV;Karpova, AY;Howley, PM
在酵母双杂交筛选中发现干扰素调节因子 3 (IRF-3) 与 HPV16 E6 特异性相互作用。 IRF-3 通过双链 RNA 的存在或病毒感染而被激活，与其他转录调节因子形成稳定的复合物，这些转录调节因子与 IFN β 启动子的调节元件结合。我们证明IRF-3是一种有效的转录激活剂，并证明HPV16 E6可以抑制其反式激活功能。仙台病毒感染后，原代人角质形成细胞中 HPV16 E6 的表达抑制 IFN β mRNA 的诱导。 HPV16 E6 与 IRF-3 的结合不会导致其泛素化或降解。我们认为，E6 与 IRF-3 的相互作用以及 IRF-3 转录活性的抑制可能为病毒提供了一种规避 HPV16 感染细胞正常抗病毒反应的方法。
Interferon regulatory factor-3 (IRF-3) was found to specifically interact with HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of double-stranded RNA or by virus infection to form a stable complex with other transcriptional regulators that bind to the regulatory elements of the IFN beta promoter. We show that IRF-3 is a potent transcriptional activator and demonstrate that HPV16 E6 can inhibit its transactivation function. The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFN beta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3 does not result in its ubiquitination or degradation. We propose that the interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional activity may provide the virus a means to circumvent the normal antiviral response of an HPV16-infected cell.