丙型肝炎病毒被膜蛋白E1信号序列的切割受下游序列的影响  

Effect of Downstream Sequence on the Cleavage of Envelop Protein 1 Signal Sequence in Hepatitis C Virus

作　　者：朱立新[1] 孔玉英[1] 汪垣[1] 李光地[1] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031

出　　处：《生物化学与生物物理学报》2001年第6期682-686,共5页

基　　金：国家高技术"86 3"计划资助项目 (No .86 3 10 2 0 7 0 2 0 2 )~~

摘　　要：在痘苗病毒 /T7系统中构建并表达了不同结构的丙型肝炎病毒 (HCV)结构蛋白质基因片段。比较不同结构中E1信号序列的切割效率 ,发现E1信号序列下游E1或E2序列缺失都降低了E1信号序列切割加工的效率。将被膜蛋白序列E1 E2替换成长度相当的 β 半乳糖苷酶序列后也降低了该位点的切割效率 ,表明完全的E1信号序列的切割与下游相对完整的被膜蛋白E1、E2序列的存在有关。计算机辅助分析发现E1信号序列是一个很典型的信号序列 ,然而 ,实验结果却表明其切割效率受其下游序列的影响。这种依赖于上下游序列的信号序列加工目前仅发现存在于IL 12信号序列加工和黄病毒C/ prM位点 (prM信号序列 )的加工。由于黄病毒和HCV均属黄病毒科 ,这种在同一科内具有相类似的异常的信号序列加工 ,其生物学意义值得深入研究。The RNA genome of hepatitis C virus encodes a polyprotein of ～3 000 amino acids, which is processed into 10 viral proteins by proteases provided by host cells and virus itself. Multiple precursors are produced due to inefficient processing. Here, the study of E1 signal sequence (C/E1 site) processing in eukaryotic vaccinia virus/T7 system is reported. Differently truncated HCV structural proteins were expressed in this system. It was found that the efficient cleavage of E1 signal sequence was affected by downstream envelop protein sequences. When the lacZ gene encoding a product with similar size was engineered downstream to the E1 signal sequence, the inefficient cleavage of signal sequence was also observed, suggesting that the effect of downstream sequence on the cleavage was due to the presence of the envelop protein sequences. Computer aided analysis clearly showed that E1 signal sequences was a typical signal sequence. The influence of downstream sequences to signal sequence cleavage demonstrated here was uncommon. To date, similar observations were only reported for the processing of IL 12 signal sequence and the C/prM site of flavivirus. As both flavivirus and HCV are classified into the same Flaviviridae family, this downstream sequence related cleavage of signal sequence worths further studying.

关 键 词：丙型肝炎病毒 HCV 信号序列 翻译后加工 被膜蛋白E1 切割加工 

分 类 号：Q753[生物学—分子生物学]