本文關(guān)鍵詞：新城疫病毒樣顆粒的構(gòu)建及免疫原性和免疫機(jī)制研究　出處：《吉林大學(xué)》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 新城疫病毒樣顆粒 樹突狀細(xì)胞 成熟 遷移 天然免疫

【摘要】：病毒樣顆粒(Virus-like particles,VLPs)是由病毒結(jié)構(gòu)蛋白裝配而成的空心蛋白顆粒,與真實(shí)病毒形態(tài)結(jié)構(gòu)相似,無(wú)自主復(fù)制能力,可作為安全有效的新型疫苗預(yù)防病毒性傳染病,近年來(lái)VLP技術(shù)已成為疫苗研究領(lǐng)域的熱點(diǎn)。新城疫病毒樣顆粒(Newcastle disease virus-like particles,NDV VLPs)是由新城疫病毒基質(zhì)蛋白(M)為病毒骨架,可裝配病毒血凝素-神經(jīng)氨酸酶(HN)、融合蛋白(F)或核蛋白(NP)。已有研究表明,NDV VLPs能誘導(dǎo)機(jī)體產(chǎn)生特異性體液和細(xì)胞免疫應(yīng)答,以及有效的免疫保護(hù)效力,這與其他VLP疫苗誘導(dǎo)的適應(yīng)性免疫應(yīng)答能力相似。然而,關(guān)于NDV VLPs如何激活天然免疫應(yīng)答的研究尚無(wú)報(bào)道。正常情況下,機(jī)體免疫系統(tǒng)識(shí)別外源抗原涉及特定的免疫細(xì)胞,如吞噬細(xì)胞或淋巴細(xì)胞。樹突狀細(xì)胞(Dendritic cells,DCs)是目前抗原遞呈能力最強(qiáng)的專職免疫細(xì)胞,在連接天然免疫與適應(yīng)性免疫之間具有獨(dú)特功能。成熟DCs(m DCs)遷移至次級(jí)淋巴組織能夠刺激初始型T細(xì)胞(Na?ve T cell)活化和增殖,被認(rèn)為是特異性免疫應(yīng)答的始動(dòng)者。因此,闡明NDV VLPs誘導(dǎo)DC成熟與遷移的免疫機(jī)制對(duì)更好地理解VLP激活的天然免疫應(yīng)答具有重要科學(xué)意義。目前,有關(guān)DC成熟與遷移的研究主要集中在小鼠等哺乳動(dòng)物模型上,雖然NDV感染的宿主為禽類,但是已經(jīng)明確禽類的免疫反應(yīng)大部分與其他生物物種相同,只是在細(xì)節(jié)上存在差異。為此,本研究以NDV VLPs與小鼠DCs為研究靶點(diǎn),利用昆蟲桿狀病毒表達(dá)系統(tǒng)組裝了NDV VLPs,通過(guò)小鼠模型分析NDV VLPs激發(fā)的體液和細(xì)胞免疫應(yīng)答水平以評(píng)價(jià)其免疫原性;利用分子生物學(xué)方法、細(xì)胞生物學(xué)分析手段以及系統(tǒng)免疫學(xué)技術(shù)體系,探討NDV VLPs誘導(dǎo)體外DC成熟與遷移的分子機(jī)制及其信號(hào)通路,揭示體內(nèi)DCs捕獲NDV VLPs后的遷移路徑及遞呈效應(yīng)。主要研究?jī)?nèi)容如下:一、本實(shí)驗(yàn)首先利用昆蟲桿狀病毒表達(dá)系統(tǒng),構(gòu)建共表達(dá)NDV結(jié)構(gòu)蛋白的重組桿狀病毒(r BV-M和r BV-M+HN),組裝并純化了NDV VLPs(M和M-HN)。免疫電鏡檢測(cè)結(jié)果可見明顯膠體金顆粒,表明NDV VLPs能與NDV HN蛋白單克隆抗體發(fā)生特異性反應(yīng),同時(shí)可見病毒顆粒具有典型的囊膜結(jié)構(gòu),與野生型NDV大小相似(100-200nm)。Western blot分析結(jié)果可見約40k Da和68k Da大小條帶,表明該顆粒還能與特異性NDV抗體發(fā)生反應(yīng)。為評(píng)價(jià)NDV VLPs在小鼠模型中的免疫原性,血凝抑制試驗(yàn)和間接ELISA法檢測(cè)結(jié)果表明VLP組可誘導(dǎo)產(chǎn)生更高的血凝抑制抗體效價(jià)和特異性Ig G抗體水平,與異源病毒(La Sota株)的反應(yīng)原性一致,同時(shí)也發(fā)現(xiàn)VLP組Ig G抗體亞型以Ig G1為主。流式細(xì)胞術(shù)檢測(cè)結(jié)果表明,VLPs可誘導(dǎo)產(chǎn)生較多的Th細(xì)胞(CD3+CD4+細(xì)胞),并且相比于WIV組能激活更多的Th1細(xì)胞(CD4+IFN-γ+細(xì)胞)和Tc細(xì)胞(CD8+IFN-γ+細(xì)胞);另外還發(fā)現(xiàn)VLPs招募了更多的DC遷移至脾臟。以上結(jié)果表明,NDV VLPs能產(chǎn)生特異性免疫應(yīng)答,這可能與招募的DC活化程度有關(guān)。二、為探索NDV VLPs誘導(dǎo)體外DC成熟與遷移的免疫機(jī)制,采用體外重組細(xì)胞因子GM-CSF和IL-4聯(lián)合誘導(dǎo)小鼠骨髓細(xì)胞分化為具有典型樹枝狀突起DCs,且表面標(biāo)志分子CD11c和MHC II符合后續(xù)實(shí)驗(yàn)的要求。以原代細(xì)胞開展系統(tǒng)性DC免疫學(xué)研究,FITC-葡聚糖吞噬實(shí)驗(yàn)結(jié)果表明DCs可有效攝取VLPs;混合淋巴細(xì)胞反應(yīng)數(shù)據(jù)說(shuō)明,VLP組DCs可促進(jìn)初始型T細(xì)胞分化,具體表現(xiàn)為Th1型(IL-2)和Th2型(IL-10)細(xì)胞因子分泌水平增加;流式細(xì)胞術(shù)檢測(cè)表面成熟標(biāo)志分子和ELISA法檢測(cè)細(xì)胞因子結(jié)果可見,VLPs能誘導(dǎo)DC上調(diào)MHC II、CD80、CD86、CD40分子的表達(dá)以及增加TNF-α、IFN-γ、IL-6、IL12p70的分泌;另外,還發(fā)現(xiàn)單獨(dú)M VLPs或是HN蛋白也能促進(jìn)炎性細(xì)胞因子的分泌,這表明完整的病毒粒子結(jié)構(gòu)和HN蛋白也可誘導(dǎo)DC成熟;然而不同組裝類型的VLPs其分泌炎性細(xì)胞因子的水平不一,推測(cè)這可能與NDV F或HN特性有關(guān)。為進(jìn)一步探討NDV VLPs誘導(dǎo)DC成熟的免疫機(jī)制及其可能的信號(hào)通路,流式細(xì)胞術(shù)和ELISA法檢測(cè)結(jié)果表明,TLR4和NF-κB抑制劑處理能降低NDV VLPs誘導(dǎo)的DC活化,表現(xiàn)為DC表面成熟標(biāo)志分子表達(dá)不同程度降低并且分泌細(xì)胞因子水平顯著減少;Western blot結(jié)果顯示NDV VLPs促進(jìn)了DC胞內(nèi)NF-κB(p65)、IκB以及IKK分子的磷酸化表達(dá),說(shuō)明VLPs誘導(dǎo)DC成熟可通過(guò)TLR4-IKK-IκB-NF-κB信號(hào)通路實(shí)現(xiàn)。與此同時(shí),VLPs可上調(diào)DC表面CCR7分子的表達(dá),而下調(diào)CCR5分子的表達(dá);進(jìn)一步采用Transwell小室法和抗體阻斷法驗(yàn)證了VLPs誘導(dǎo)DC遷移依賴于CCR7-CCL19/CCL21軸的作用,并且CCL21的作用更為顯著。三、為了揭示NDV VLPs誘導(dǎo)體內(nèi)DC成熟與遷移的細(xì)胞與分子機(jī)制,本實(shí)驗(yàn)先采用CFSE標(biāo)記m DCs經(jīng)尾靜脈過(guò)繼回輸給小鼠,流式細(xì)胞術(shù)檢測(cè)引流淋巴結(jié)和脾臟并結(jié)合ELISA法測(cè)定趨化因子結(jié)果表明,m DCs在體內(nèi)的遷移仍是依賴CCL19和CCL21的濃度差作用,負(fù)載VLPs的DCs可促進(jìn)淋巴組織中CCL19和CCL21的分泌,并且CCL21對(duì)m DC遷移更為重要;最終通過(guò)流式細(xì)胞術(shù)檢測(cè)細(xì)胞表型以及胞內(nèi)細(xì)胞因子結(jié)果顯示m DC組各亞型T細(xì)胞顯著高于im DC組和PBS組,表明該m DCs能夠在體內(nèi)激活脾臟T細(xì)胞并向各亞群分化。為了模擬真實(shí)VLPs在體內(nèi)被處理加工的過(guò)程,本實(shí)驗(yàn)另外也注射VLPs至小鼠足底,結(jié)果表明VLPs早期招募DCs在引流淋巴結(jié)聚集,而隨著時(shí)間推移,脾臟DCs的百分比上升,推測(cè)DC是由外周組織經(jīng)引流淋巴結(jié)向脾臟遷移,而72h后脾臟T、B淋巴細(xì)胞活化和增殖導(dǎo)致DC百分占比率降低。另外,胞內(nèi)細(xì)胞因子染色結(jié)果表明僅Th型(CD4+IFN-γ+和CD4+IL-4+)細(xì)胞產(chǎn)生了分化,說(shuō)明VLPs被體內(nèi)DCs攝取進(jìn)而激活初始型T細(xì)胞。以上結(jié)果顯示,VLPs能誘導(dǎo)體內(nèi)DC經(jīng)由引流淋巴結(jié)遷移至脾臟,進(jìn)而促使初始型T細(xì)胞活化和分化。綜上所述,本研究組裝了NDV VLPs,該顆粒具有良好的免疫原性;揭示NDV VLPs誘導(dǎo)體內(nèi)、外DC成熟與遷移的免疫機(jī)制,為深入闡明VLPs激活天然免疫應(yīng)答機(jī)制提供科學(xué)依據(jù)。
[Abstract]:Virus like particles (Virus-like, particles, VLPs) is hollow particles by protein structure protein of virus assembly, similar to the real virus morphology, no self replication ability, can be used as a safe and effective vaccine to prevent viral infectious disease in recent years, VLP technology has become a hot research field for vaccine of Newcastle disease virus like. The particles (Newcastle disease virus-like particles, NDV VLPs) by Newcastle disease virus matrix protein (M) virus skeleton assembly virus hemagglutinin neuraminidase (HN), fusion protein (F) or nuclear protein (NP). Studies have shown that NDV VLPs can induce specific humoral and cellular immune responses. And the effective immune protection effect, which induced by VLP vaccine and other adaptive immune response is similar. However, there are few research reports about NDV VLPs how to activate the innate immune response. Under normal circumstances, machine Specific immune cells involved in the immune system to recognize the foreign body antigen, such as macrophages or lymphocytes. Dendritic cells (Dendritic cells DCs) is currently a full-time antigen presenting immune cells has the strongest ability, in the connection between innate immunity and adaptive immunity unique function. The mature DCs (m DCs) can stimulate migration to secondary lymphoid tissue the initial T cell (Na ve? T cell) activation and proliferation, is considered to be the initiator of specific immune response. Therefore, clarifying the mechanism of NDV VLPs immune maturation and migration induced by DC has important scientific significance for a better understanding of the innate immune response activated by VLP. At present, the research on DC maturation and migration of the main in mice and other mammals model, although the NDV infected host for poultry, but has a clear immune response of poultry and other biological species, most of the same, but the details are poor Different. Therefore, in this study, NDV VLPs and DCs mice as the research target, using insect baculovirus expression system was assembled NDV VLPs, to evaluate the immunogenicity of NDV VLPs cells and stimulate the humoral immune response level by mouse model analysis; with the method of molecular biology, cell biology and Immunology technology system system analysis method to explore the molecular mechanism of NDV and VLPs in vitro maturation and migration induced by DC and its signal transduction pathway, migration path to capture NDV after VLPs and DCs revealed in presenting effect. The main research contents are as follows: first, this study first used the insect baculovirus expression system, recombinant baculovirus coexpressing NDV structural proteins (R and BV-M R BV-M+HN), the assembly and the purification of NDV (M VLPs and M-HN). Immune electron microscopy results showed that the colloidal gold particles, NDV VLPs and NDV HN protein monoclonal antibody specific against At the same time, visible viral particles with envelope structure typical, similar to wild type NDV (100-200nm).Western size blot analysis results about 40K Da and 68K Da visible stripe, but also shows that the particles with specific NDV antibody reaction. For evaluation of NDV VLPs in a mouse model of immunogenicity, blood coagulation inhibition test and indirect ELISA assay results show that VLP can induce higher hemagglutination inhibition antibody titer and specificity of Ig G antibody level, with heterologous virus (La strain Sota) the reactionogenicity, also found that group VLP Ig G to Ig G1 antibody subtype. Flow cytometry the results show that VLPs can induce more Th cells (CD3+CD4+ cells), and compared to the WIV group can activate more Th1 cells (CD4+IFN- + cells) and Tc cells (CD8+IFN- + cells); it is also found that VLPs recruited more DC migrate to the node above the spleen. The results show that NDV VLPs can produce specific immune response, which may be related to the recruitment of DC activation degree. Two, to explore the mechanism of NDV VLPs DC in vitro immune maturation and migration induced by in vitro, recombinant cytokines GM-CSF and IL-4 combination induced differentiation of bone marrow cells in mice with typical dendritic processes of DCs, and the surface markers CD11c and MHC II in accordance with the requirements of the following experiment. To carry out the research of DC system based on immunology primary cells, FITC- glucan phagocytosis experiment results show that DCs can effectively absorb VLPs data; mixed lymphocyte reaction, VLP group of DCs may promote the differentiation of naive T cells, the specific performance of Th1 type (IL-2) and Th2 (IL-10) the secretion of cytokines were increased; the detection of surface markers of molecules and ELISA cytokines were measured by flow cytometry showed that VLPs could induce the upregulation of MHC, DC II, CD80, CD86, CD40 and increase the expression of the son TNF- alpha, IFN- gamma, IL-6, IL12p70 secretion; in addition, also found that M alone VLPs or HN protein can promote the secretion of inflammatory cytokines, suggesting that the virus particle structure and complete HN protein can also induce DC maturation; however, different types of VLPs assembled the secretion of inflammatory cytokines no, NDV and F speculate that this may or HN characteristics. To further explore the NDV signaling pathway in VLPs induced immune mechanism of DC maturation and the possibility of the flow cytometry and ELISA assay showed that TLR4 and NF- kappa B inhibitor NDV treatment could reduce VLPs induced DC activation, as mature DC surface molecules different expression levels decreased and cytokine secretion was significantly reduced Western blot signs; results showed that NDV VLPs promoted DC intracellular NF- kappa B (p65), the expression of I kappa B and IKK molecules. The phosphorylation of VLPs induced by B-NF- DC mature TLR4-IKK-I kappa kappa B The signal pathway of VLPs. At the same time, DC can up regulate the expression of CCR7 molecules on the surface, and the expression of CCR5 molecules; further using Transwell assay and antibody blocking method to verify the VLPs induced DC migration depends on the role of CCR7-CCL19/CCL21 axis, and the effect of CCL21 is more significant. Three, in order to reveal the cellular and molecular mechanisms of NDV VLPs in vivo maturation and migration induced by DC, the first experiment using CFSE labeled m DCs via intravenous adoptive transfer to mice, flow cytometry in draining lymph nodes and spleen combined with ELISA method for the determination of chemokines results showed that the concentration of M is still in the migration of DCs in CCL19 dependent and CCL21 difference, VLPs load the DCs can promote the secretion of CCL19 and CCL21 in lymphoid tissues, and CCL21 of the m DC migration is more important; finally through flow cytometry to detect the phenotype and intracellular cytokines showed m DC in each group Subtype of T cells was significantly higher than that of im DC group and PBS group, indicating that the m DCs can be activated in vivo spleen T cell subsets and differentiation. In order to simulate the process of VLPs in vivo was processed, this experiment also injected VLPs mice to the foot, the results show that the VLPs early recruitment of DCs gathered in the draining lymph node however, with the passage of time, the percentage of DCs in spleen increased, suggesting that DC is a peripheral tissue by draining lymph nodes to the spleen and spleen after migration, 72h T, B lymphocyte activation and proliferation in DC percent ratio decreased. In addition, intracellular cytokine staining results showed that only Th (CD4+IFN- + and CD4+IL-4+) cells produced a differentiation, indicating that VLPs is in DCs uptake and activation of naive T cells. These results showed that VLPs could induce DC in vivo via lymph nodes migrate to the spleen, which prompted the initial T cell activation and differentiation. To sum up, this research The NDV VLPs was assembled. The particle has good immunogenicity. It reveals the immune mechanism of NDV VLPs inducing the maturation and migration of DC in vivo and in vitro, and provides a scientific basis for further elucidating the mechanism of VLPs activating the innate immune response.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：S852.4

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李增光;什么是新城疫病毒的腦內(nèi)致病指數(shù)[J];山東家禽;2001年04期

2 ;智利鳥類感染新城疫病毒[J];中國(guó)家禽;2007年14期

3 顧有方;操志鋒;陳會(huì)良;王玨;路振香;李文超;胡元慶;張訓(xùn)海;;異源新城疫病毒感染對(duì)雛鴨組織抗氧化酶活性的影響[J];中國(guó)獸醫(yī)學(xué)報(bào);2008年11期

4 初莉莉;王治德;李術(shù)梅;劉躍光;于彥強(qiáng);;新城疫病毒分子生物學(xué)研究進(jìn)展[J];中國(guó)畜禽種業(yè);2009年11期

5 李增光;什么是新城疫病毒的基因型──從去冬今春的雞群病情談起[J];山東家禽;2000年06期

6 盧建紅,談志祥,魯杏華,邱立新,元瓊香;應(yīng)用聚乙二醇介導(dǎo)的單抗夾心ELISA監(jiān)測(cè)湖南新城疫病毒強(qiáng)毒感染[J];湖南農(nóng)業(yè)大學(xué)學(xué)報(bào)(自然科學(xué)版);2001年05期

7 瞿國(guó)潤(rùn),吳艷濤,張如寬,劉秀梵;我國(guó)部分地區(qū)新城疫病毒分子流行病學(xué)研究[J];中國(guó)獸醫(yī)科技;2001年03期

8 劉華雷,王永坤,嚴(yán)維巍,朱國(guó)強(qiáng),周繼宏,田慧芳;中國(guó)部分地區(qū)新城疫病毒的分子流行病學(xué)研究[J];揚(yáng)州大學(xué)學(xué)報(bào)(自然科學(xué)版);2001年01期

9 李增光;什么是新城疫病毒的基因型——從去冬今春的雞群病情說(shuō)起[J];中國(guó)動(dòng)物保健;2001年05期

10 王忠田,王澤霖,陳溥言,楊漢春;新城疫病毒分子生物學(xué)最新研究進(jìn)展[J];動(dòng)物醫(yī)學(xué)進(jìn)展;2002年02期

相關(guān)會(huì)議論文 前10條

1 魯會(huì)軍;劉昊;張丹;金擴(kuò)世;金寧一;;新城疫病毒進(jìn)化與跨種感染[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)家畜傳染病學(xué)分會(huì)第七屆全國(guó)會(huì)員代表大會(huì)暨第十三次學(xué)術(shù)研討會(huì)論文集（上冊(cè)）[C];2009年

2 孫玉章;母連志;丁壯;;新城疫病毒載體的研究及應(yīng)用進(jìn)展[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)家畜傳染病學(xué)分會(huì)第七屆全國(guó)會(huì)員代表大會(huì)暨第十三次學(xué)術(shù)研討會(huì)論文集（上冊(cè)）[C];2009年

3 楊帆;岳華;湯承;侯巍;;靶向新城疫病毒NP基因shRNA重組腺病毒載體的構(gòu)建[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)禽病學(xué)分會(huì)第十四次學(xué)術(shù)研討會(huì)論文集[C];2008年

4 劉華雷;王志亮;吳延功;鄭東霞;孫承英;趙云玲;徐天剛;;2002-2007年355株中國(guó)新城疫病毒分子流行病學(xué)分析[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)禽病學(xué)分會(huì)第十四次學(xué)術(shù)研討會(huì)論文集[C];2008年

5 任濤;王琴;羅開健;張桂紅;廖明;;新城疫病毒單克隆抗體的制備及鑒定[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)畜牧獸醫(yī)生物技術(shù)學(xué)分會(huì)暨中國(guó)免疫學(xué)會(huì)獸醫(yī)免疫分會(huì)第七次研討會(huì)論文集[C];2008年

6 孟春春;張向樂(lè);孫英杰;仇旭升;陳鴻軍;于圣青;丁鏟;;新城疫病毒感染腫瘤細(xì)胞后能誘導(dǎo)自噬的發(fā)生[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)獸醫(yī)公共衛(wèi)生學(xué)分會(huì)第三次學(xué)術(shù)研討會(huì)論文集[C];2012年

7 胡增壘;胡順林;胡嬌;宋慶慶;丁平云;朱杰;劉曉文;王曉泉;劉秀梵;;基因Ⅶd亞型新城疫病毒高度侵害雞免疫系統(tǒng)的重要機(jī)制[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)禽病學(xué)分會(huì)第十六次學(xué)術(shù)研討會(huì)論文集[C];2012年

8 劉家國(guó);徐玉鳳;趙彪;王德云;范云鵬;胡元亮;;板藍(lán)根生物堿酸性部位對(duì)新城疫病毒吸附、釋放的影響[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)2010年學(xué)術(shù)年會(huì)——第二屆中國(guó)獸醫(yī)臨床大會(huì)論文集(下冊(cè))[C];2010年

9 瞿國(guó)潤(rùn);吳艷濤;張如寬;劉秀梵;;我國(guó)部分地區(qū)新城疫病毒分子流行病學(xué)及其生物學(xué)特性的研究[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)禽病學(xué)會(huì)分會(huì)第十次學(xué)術(shù)研討會(huì)論文集[C];2000年

10 劉華雷;王永坤;嚴(yán)維巍;朱國(guó)強(qiáng);;我國(guó)部分地區(qū)新城疫病毒的流行現(xiàn)狀分析[A];中國(guó)畜牧獸醫(yī)學(xué)會(huì)禽病學(xué)分會(huì)第十一次學(xué)術(shù)研討會(huì)論文集[C];2002年

相關(guān)重要報(bào)紙文章 前5條

1 哈冰;揭開新城疫病毒奧秘的曹殿軍[N];農(nóng)民日?qǐng)?bào);2001年

2 秦衛(wèi)紅;種鵝感染新城疫病毒的診斷[N];中國(guó)畜牧獸醫(yī)報(bào);2013年

3 寧啟文;我國(guó)研制成功H5亞型禽流感重組新城疫病毒活載體雙價(jià)疫苗[N];農(nóng)民日?qǐng)?bào);2005年

4 劉萬(wàn)珍;哪些畜禽不能混養(yǎng)[N];農(nóng)民日?qǐng)?bào);2013年

5 ;夏季怎樣提高養(yǎng)雞效益[N];中國(guó)畜牧獸醫(yī)報(bào);2008年

相關(guān)博士學(xué)位論文 前10條

1 郝華芳;新城疫病毒V蛋白結(jié)合MDA5抑制DF-1細(xì)胞IFN-β生成的功能域研究[D];西北農(nóng)林科技大學(xué);2015年

2 朱杰;2008-2013年華東地區(qū)新城疫病毒分子流行病學(xué)及HN基因E347K變異對(duì)病毒抗原性的影響[D];揚(yáng)州大學(xué);2015年

3 曹永忠;新城疫病毒生物信息分析系統(tǒng)的構(gòu)建及其全基因組的比較研究[D];揚(yáng)州大學(xué);2009年

4 王元;重組新城疫病毒rNDV-18HL的構(gòu)建及抗腫瘤靶向作用機(jī)制研究[D];第四軍醫(yī)大學(xué);2014年

5 孫英杰;新城疫病毒誘導(dǎo)宿主細(xì)胞應(yīng)激顆粒形成機(jī)制的研究[D];中國(guó)農(nóng)業(yè)科學(xué)院;2015年

6 于曉慧;聚合酶相關(guān)蛋白在基因Ⅶ型新城疫病毒致病性中的作用[D];中國(guó)農(nóng)業(yè)大學(xué);2017年

7 靳繼惠;HN蛋白的來(lái)源和長(zhǎng)度對(duì)新城疫病毒生物學(xué)特性的影響[D];中國(guó)農(nóng)業(yè)大學(xué);2017年

8 錢晶;新城疫病毒樣顆粒的構(gòu)建及免疫原性和免疫機(jī)制研究[D];吉林大學(xué);2017年

9 李曉霞;新城疫病毒氣溶膠發(fā)生與傳染機(jī)制及其在生產(chǎn)雞舍環(huán)境中的監(jiān)測(cè)[D];山東農(nóng)業(yè)大學(xué);2009年

10 程相朝;新城疫病毒地方株分子流行病學(xué)調(diào)查及其疫病控制[D];南京農(nóng)業(yè)大學(xué);2003年

相關(guān)碩士學(xué)位論文 前10條

1 孫娜娜;表達(dá)雞傳染性喉氣管炎病毒gI和gB基因的重組新城疫病毒的研究[D];中國(guó)農(nóng)業(yè)科學(xué)院;2015年

2 王海新;新城疫病毒蛋白特異性抗血清的研制[D];西北農(nóng)林科技大學(xué);2015年

3 劉蓬;中國(guó)中部候鳥遷徙區(qū)基因Ⅸ型新城疫病毒的分離鑒定與遺傳進(jìn)化分析[D];西北農(nóng)林科技大學(xué);2015年

4 祁芳;表達(dá)雞傳染性喉氣管炎病毒gB基因重組新城疫病毒的構(gòu)建及其拯救[D];南京農(nóng)業(yè)大學(xué);2012年

5 梁殊林;表達(dá)新城疫病毒HN蛋白重組鴨腸炎病毒的構(gòu)建[D];東北農(nóng)業(yè)大學(xué);2015年

6 吳偉;鴨源新城疫病毒部分中國(guó)分離株生物學(xué)特性研究[D];東北農(nóng)業(yè)大學(xué);2015年

7 張婷婷;兩種不同來(lái)源新城疫病毒的感染對(duì)雞免疫作用的分子機(jī)制[D];東北農(nóng)業(yè)大學(xué);2015年

8 徐倩倩;鵝源新城疫病毒感染對(duì)鵝免疫功能作用的分子機(jī)制[D];東北農(nóng)業(yè)大學(xué);2015年

9 王曉旭;新城疫病毒誘導(dǎo)宿主細(xì)胞應(yīng)激顆粒形成機(jī)制的初步探究[D];安徽農(nóng)業(yè)大學(xué);2014年

10 丁云磊;新城疫病毒降解線粒體抗病毒信號(hào)蛋白MAVS的機(jī)制研究[D];南京農(nóng)業(yè)大學(xué);2014年

，

本文編號(hào)：1363541