Cross-talk between viral. infection and bacterial infection in oral region

在本研究中，我们证实toll样受体2 （TLR2）参与人类腺病毒5型（Ad5）的识别，并通过TLR2途径抑制腺病毒E1A对NF-κB活化的作用。突变分析显示，腺病毒E1A通过两个独立的途径抑制NF-κB的激活，包括转录共激活因子p300和转录因子E2Fs。NF-κB抑制的分子机制可以解释为E1A和NF-κB之间竞争有限数量的核p300/CBP共激活子，或者RelA/ p65与E2Fs之间形成复合物，E1A通过与Rb蛋白的竞争性结合而取代Rb家族蛋白。RelA/ p65和E2F之间复合物的形成也消除了E2F依赖性的转录激活。结果表明，人腺病毒具有NF-κB /Rel家族和E2F家族蛋白的转录干扰策略，并利用该策略激活宿主细胞周期，抑制宿主先天免疫反应。

In the present study, we demonstrated the involvement of toll-like receptor 2 (TLR2) in the recognition of human adenovirus type 5 (Ad5) and the repressive effect of adenovirus E1A to the NF-κB activation via TLR2 pathways. Mutational analysis revealed that adenovirus E1A inhibited the NF-κB activation utilizing two independent pathways involving transcriptional co-activator p300 and the transcription factor E2Fs. Molecular mechanism of the NF-κB repression was explained by the competition between E1A and NF-κB for the limited amount of nuclear p300/CBP coactivator or the complex formation between RelA/ p65 and E2Fs which are displaced from Rb family proteins by competitive E1A binding to Rb proteins. The complex formation between RelA/ p65 and E2Fs also abolished the E2F dependent transcriptional activation. It is revealed that human adenovirus possess the transcriptional interference strategy involving NF-κB /Rel family and E2F family proteins and that human adenovirus utilize the strategy for the activation of host cell cycle and the repression of host innate immunological response.