甲型和乙型流感病毒M2离子通道作为抗病毒靶点的研究

发布时间：2018-05-25 03:07

本文选题：流感病毒 + M2　；参考：《华东师范大学》2011年硕士论文

【摘要】：为了制备和筛选针对甲型和乙型流感病毒具有广谱和强抗病毒活力的抗体和多肽,我们应用杂交瘤技术分别制备了针对甲型流感病毒M2和乙型流感病毒BM2离子通道的单克隆抗体,同时应用噬菌体展示技术筛选出与乙型流感病毒M2离子通道膜外区高特异结合的噬菌体多肽,并分别从细胞水平上研究了它们的抗病毒活性。结果分别筛选到针对甲型和乙型流感病毒M2膜外区N末端8个保守氨基酸序列的单克隆抗体M2e8-7和BM2e-2,其中M2e8-7抗体高特异性结合已知21种甲型流感病毒M2突变型中的19种,是已报道的M2单克隆抗体中识别病毒种类最多的一株抗体。病毒中和实验显示M2e8-7能有效抑制所识别的不同甲型流感病毒突变型在MDCK细胞里的复制。与此类似,BM2e-2抗体有效抑制了不同乙型流感病毒株在MDCK细胞里的复制。此外,还筛选到了能与乙型流感病毒M2膜外区8个保守氨基酸序列高度特异结合的短肽VSFTPSF,其抗病毒活性还有待进一步研究。因此,M2离子通道的独特结构对于抗病毒感染具有重要的作用,本研究所筛选到的针对甲型和乙型流感病毒特异的单克隆抗体和短肽为临床检测和抗病毒药物的开发提供了重要的理论依据。
[Abstract]:In order to prepare and screen antibodies and peptides against influenza A and B viruses with broad spectrum and strong antiviral activity, We have prepared monoclonal antibodies against BM2 ion channels of influenza A virus M2 and influenza B virus respectively using hybridoma technique. At the same time, phage peptides with high specific binding to the extracellular region of M2 ion channel of influenza B virus were screened by phage display technique, and their antiviral activities were studied at the cell level. Results Monoclonal antibodies M2e8-7 and BM2e-2 were screened for 8 conserved amino acid sequences of the outside region of M2 of influenza A and B influenza virus respectively. Among them, 19 of the 21 known M2 mutants of influenza A virus were specifically bound by M2e8-7 antibody. It is one of the most reported monoclonal antibodies to M 2 that recognize virus types. Virus neutralization test showed that M2e8-7 could effectively inhibit the replication of different influenza A virus mutants in MDCK cells. Similarly, BM2e-2 antibody effectively inhibited the replication of different influenza B virus strains in MDCK cells. In addition, a short peptide, VSFTPSF, which was highly specific to 8 conserved amino acid sequences of influenza B virus M2 was screened, and its antiviral activity remains to be further studied. Therefore, the unique structure of the M2 ion channel plays an important role in antiviral infection. Monoclonal antibodies and short peptides against influenza A and B viruses selected in this study provide important theoretical basis for clinical detection and development of antiviral drugs.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392

【共引文献】