论文部分内容阅读
卡波氏肉瘤相关疱疹病毒(Kaposi’s sarcoma-associated herpesvirus,KSHV),又称人类疱疹病毒8型(Human herpesvirus 8,HHV-8),是艾滋病感染者中发病率最高的肿瘤-卡波氏肉瘤的致病性病原体。本实验对KSHV裂解期蛋白-病毒白细胞介素6(Viral interleukin-6,vIL-6)抑制宿主固有免疫机制进行初步探讨。利用仙台病毒刺激人胚肾细胞(HEK293T)激活抗病毒固有免疫,观察vIL-6过表达后对IFN-β的作用及机制,利用实时定量PCR检测IFN-β基因表达及双荧光素酶实验分析IFN-β基因启动子的活性。过表达vIL-6后,IFN-β基因mRNA水平表达明显下降,进一步实验证明vIL-6可抑制IFN-β基因启动子活性,且vIL-6可特异性作用于IFN-β基因启动子PRDIII-PRDI区。本研究首次证实了KSHV vIL-6可通过抑制IFN-β启动子活性从而调控IFN-β表达,且这种作用主要通过IRF-3信号途径。
Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the most prevalent form of HIV-1 infection in Kaposi’s sarcoma Pathogenic pathogen. In this study, we explored the mechanism of vIL-6, an inhibitor of KSHV, in the host immune system. The anti-virus innate immunity was stimulated by Sendai virus-stimulated human embryonic kidney (HEK293T) cells. The effect and mechanism of IFN-β after vIL-6 overexpression were observed. Real-time quantitative PCR was used to detect IFN-β gene expression and dual luciferase assay IFN-β gene promoter activity. After vIL-6 was overexpressed, the expression of IFN-β mRNA was significantly decreased. Further experiments showed that vIL-6 could inhibit the activity of IFN-β promoter, and vIL-6 could specifically affect the expression of IFN-β promoter PRDIII- PRDI area. This study demonstrated for the first time that KSHV vIL-6 regulates IFN-β expression by inhibiting the activity of IFN-β promoter, and this effect is mainly mediated by the IRF-3 signaling pathway.