甲型和乙型流感病毒M2離子通道作為抗病毒靶點(diǎn)的研究
發(fā)布時(shí)間:2018-05-25 03:07
本文選題:流感病毒 + M2 ; 參考:《華東師范大學(xué)》2011年碩士論文
【摘要】:為了制備和篩選針對(duì)甲型和乙型流感病毒具有廣譜和強(qiáng)抗病毒活力的抗體和多肽,我們應(yīng)用雜交瘤技術(shù)分別制備了針對(duì)甲型流感病毒M2和乙型流感病毒BM2離子通道的單克隆抗體,同時(shí)應(yīng)用噬菌體展示技術(shù)篩選出與乙型流感病毒M2離子通道膜外區(qū)高特異結(jié)合的噬菌體多肽,并分別從細(xì)胞水平上研究了它們的抗病毒活性。結(jié)果分別篩選到針對(duì)甲型和乙型流感病毒M2膜外區(qū)N末端8個(gè)保守氨基酸序列的單克隆抗體M2e8-7和BM2e-2,其中M2e8-7抗體高特異性結(jié)合已知21種甲型流感病毒M2突變型中的19種,是已報(bào)道的M2單克隆抗體中識(shí)別病毒種類最多的一株抗體。病毒中和實(shí)驗(yàn)顯示M2e8-7能有效抑制所識(shí)別的不同甲型流感病毒突變型在MDCK細(xì)胞里的復(fù)制。與此類似,BM2e-2抗體有效抑制了不同乙型流感病毒株在MDCK細(xì)胞里的復(fù)制。此外,還篩選到了能與乙型流感病毒M2膜外區(qū)8個(gè)保守氨基酸序列高度特異結(jié)合的短肽VSFTPSF,其抗病毒活性還有待進(jìn)一步研究。因此,M2離子通道的獨(dú)特結(jié)構(gòu)對(duì)于抗病毒感染具有重要的作用,本研究所篩選到的針對(duì)甲型和乙型流感病毒特異的單克隆抗體和短肽為臨床檢測(cè)和抗病毒藥物的開發(fā)提供了重要的理論依據(jù)。
[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.
【學(xué)位授予單位】:華東師范大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2011
【分類號(hào)】:R392
【共引文獻(xiàn)】
相關(guān)博士學(xué)位論文 前1條
1 劉彥;日本血吸蟲脫尾活童蟲表膜結(jié)合肽的親和篩選與功能鑒定[D];中南大學(xué);2011年
相關(guān)碩士學(xué)位論文 前1條
1 魏琦;日本血吸蟲肝期童蟲表膜結(jié)合多肽的篩選與初步鑒定[D];中南大學(xué);2010年
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