摘要
丙型肝炎病毒 (HCV)属于黄病毒属 ,基因组为单股正链RNA ,其致病机制与DNA病毒和逆转录病毒截然不同。由于诱导中和抗体的抗原表位恰好位于其包膜抗原E2蛋白的高变区 1(HVR1) ,因而容易逃避机体的免疫监视 ,形成慢性感染 ,同时造成发展广谱预防性疫苗的困难。噬菌体表面展示技术和模拟表位的理论和技术 ,是构建新型蛋白或基因疫苗 ,克服这一困难的可能途径。HCV基因复制和翻译有关的调节基因序列与肝细胞来源的蛋白质之间相互作用的研究 ,将有助于阐明HCV调节机制和相对嗜肝特性的分子生物学基础 ;HCV特异性受体的研究 ,将有助于阐明HCV感染并进入肝细胞的各个细节 ;酵母双杂交技术对于HCV结构和非结构蛋白结合的肝细胞蛋白的筛选 ,以抑制性消减杂交 (SSH)技术对HCV蛋白调节的肝细胞靶基因的筛选 ,将有助于阐明HCV与肝细胞大分子之间相互作用的分子机制。所有这些 ,将为最终揭密HCV感染引起慢性病毒性肝炎、肝纤维化、肝细胞癌、肝脏脂肪变、B细胞淋巴瘤、冷球蛋白血症等的分子生物学机制 ,并为反义技术、人源化单链可变区抗体为目的基因的细胞内免疫基因治疗和治疗性基因疫苗等抗HCV治疗新型方法的研究奠定了坚实的基础。
The pathogenesis of hepatitis C virus (HCV) is different from that of DNA virus and retrovirus. The epitope inducing neutralizing antibody in high variable region 1 (HVR1) is the reason for escape of host immune surveillance, evolution of chronic infection, and also difficulty of producing wide spectrum vaccine. Mimotope selected by using phage display technique is an alternative to solve this problem. The study on the binding protein to non coding region of HCV RNA is helpful to uncover the regulation of replication and translation of HCV genome. A study of the specific receptor of HCV is important to elucidate the mechanism of how HCV enter the hepatocyte. Yeast two hybrid is a useful technique to study the protein protein interactions between HCV and hepatocyte. Suppressive subtraction hybridization is an efficient method for identification of genes of interest transactivated by HCV structural and non structural proteins. All these studies will finally resulted in the full understanding of HCV pathogenesis, and will supply unique opportunity for the development of a new therapy for HCV infection.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2003年第1期23-27,共5页
Medical Journal of Chinese People's Liberation Army
