SARS冠状病毒3a蛋白通过与CAML分子结合而抑制细胞凋亡

发布时间：2018-03-17 08:06

本文选题：SARS冠状病毒　切入点：3a蛋白　出处：《中国人民解放军军事医学科学院》2005年硕士论文　论文类型：学位论文

【摘要】：与其他冠状病毒相比,SARS冠状病毒(SARS-CoV)有很强的致病性。SARS病毒的这一特点必然与其独特的基因结构有关。生物信息学分析表明,SARS病毒含有与其它冠状病毒相似的S,N,E,M等结构基因以及编码复制酶的基因。除此之外,SARS病毒还含有9个可能的非结构基因,为SARS病毒所独有,因而这些基因很可能与SARS病毒较强的致病性有关。本研究中,我们对SARS病毒9个可能的非结构蛋白中最大的一个,即3a蛋白,进行了深入的探索。免疫组化分析表明,该蛋白确实表达于SARS病毒感染的Vero E6细胞中。激光共聚焦显微分析进一步证明该蛋白定位于线粒体上。通过酵母双杂交方法,3a蛋白被证明可与定位于内质网上的一个蛋白calcium-modulating cyclophilin ligand(CAML)相结合。表达3a蛋白的CHO细胞对于细胞凋亡有较强的抵抗作用。当用siRNA抑制CAML的表达时,3a蛋白即失去对细胞凋亡的抑制作用,表明3a蛋白是通过与CAML结合而发挥其抑制细胞凋亡的作用。3a蛋白的这一功能可能与SARS病毒较强的致病性相关。当病毒侵入宿主细胞后,被感染的细胞能被宿主的免疫系统识别,并通过诱导细胞凋亡而对感染了病毒的细胞加以清除。但是在选择压力的作用下,许多病毒已经进化出某些可以逃避细胞凋亡的机制,使得病毒在宿主细胞死亡之前能完成其复制周期。另外,卡氏肉瘤相关病毒(KSHV)的K7蛋白也具有与3a蛋白类似的功能,即通过与CAML的结合而抑制细胞凋亡。通过CAML分子调节Ca~(2+)离子信号通路,可能是病毒对抗细胞凋亡的一个普遍的机制。
[Abstract]:Compared with other coronaviruses, SARS-CoV) has a strong pathogenicity. This characteristic of SARS virus must be related to its unique gene structure. Bioinformatics analysis shows that SARS virus contains a similar to other coronaviruses, such as SARS-CoV and so on. Structural genes and genes encoding replicases. In addition to SARS viruses, there are nine possible non-structural genes. It is unique to SARS virus, so these genes may be related to the strong pathogenicity of SARS virus. In this study, we explored the largest of the nine possible nonstructural proteins of SARS virus, the 3a protein. The protein was indeed expressed in Vero E6 cells infected with SARS virus. Laser confocal microscopy further demonstrated that the protein was located on mitochondria. It was proved by yeast two-hybrid method that the protein could be located in endoplasmic reticulum. CHO cells expressing 3a protein have strong resistance to apoptosis. When siRNA inhibits the expression of CAML, it loses its inhibitory effect on apoptosis. It is suggested that the function of 3a protein in inhibiting apoptosis by binding to CAML may be related to the strong pathogenicity of SARS virus. When the virus invades the host cell, the infected cell can be recognized by the host immune system. And by inducing apoptosis, the cells infected with the virus are cleared. But under selective pressure, many viruses have evolved some mechanisms that can escape apoptosis. This allows the virus to complete its replication cycle before the host cell dies. In addition, the K7 protein of KSHV has a similar function to the 3a protein. That is to say, the inhibition of cell apoptosis through the binding with CAML and the regulation of Ca~(2) ion signaling pathway by CAML may be a universal mechanism of virus anti-apoptosis.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R373

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