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

在本研究中，我们证实了Toll样受体2(Toll-like Receptor 2，TLR2)参与了人腺病毒5型(Ad5)的识别，以及腺病毒E1a通过Toll样受体2途径抑制了NF-κB的激活。突变分析表明，腺病毒E1a通过转录共激活因子p300和转录因子E2FS两条独立的途径抑制了NF-κB的激活。通过E1a和NF-κB竞争有限数量的核p300/κ共激活子，或通过竞争E1a与Rb蛋白的结合而取代Rb家族蛋白的RelA/p65和E2F之间形成复合体，解释了NF-CBP B抑制的分子机制。RelA/p65和E2FS之间的复合体的形成也取消了E2F依赖的转录激活。结果表明，人腺病毒具有转录干扰策略，涉及NF-κB/Rel家族和E2F家族蛋白；人腺病毒利用该策略激活宿主细胞周期，抑制宿主的天然免疫应答。

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.