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| 1 | 禽流感病毒血凝素保守氨基酸对其受体结合位点的影响显示文摘采用PCR定点突变技术,对H5N1亚型禽流感病毒的血凝素HA基因受体结合位点相关的保守氨基酸分别进行以下位点的定点突变:35位K→R、45位D→N、98位Y→F、193位K→R和267位A→T,构建突变表达载体pCI-HA,转染293T细胞进行瞬时表达。流式细胞检测结果显示:193位K→R的突变体的HA的表达显著增加;98位Y→F突变体的HA的表达受到显著抑制。同时,血球吸附试验表明,同一HA突变体吸附鸡红细胞和马红细胞时,显示出不同的红细胞吸附能力。因此,受体结合位点相关的193位和98位的保守氨基酸不仅对受体结合位点结构域的形成有影响,它们还在决定AIV感染的宿主特异性中具有重要的作用。 | 贾红玲 苏艳 吴润 | 2008 | 中国预防兽医学报2008，30，7： | 13 |
| 2 | Role of Positive Selection Pressure on the Evolution of H5N1 Hemagglutinin显示文摘The surface glycoprotein hemagglutinin (HA) helps the influenza A virus to evade the host immune system by antigenic variation and is a major driving force for viral evolution. In this study, the selection pressure on HA of H5N1 influenza A virus was analyzed using bioinformatics algorithms. Most of the identified positive selection (PS) sites were found to be within or adjacent to epitope sites. Some of the identified PS sites are consistent with previous experimental studies, providing further support to the biological significance of our findings. The highest frequency of PS sites was observed in recent strains isolated during 2005–2007. Phylogenetic analysis was also conducted on HA sequences from various hosts. Viral drift is almost similar in both avian and human species with a progressive trend over the years. Our study reports new mutations in functional regions of HA that might provide markers for vaccine design or can be used to predict isolates of pandemic potential. | Venkata R.S.K. Duvvuri Bhargavi Duvvuri Wilfred R. Cuff Gillian E. Wu Jianhong Wu | 2009 | Genomics, Proteomics & Bioinformatics2009，7，1： | 6 |
| 3 | Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking显示文摘The H5N1 avian influenza virus (AIV) has widely spread in Asia, Europe and Africa, making a large amount of economic loss. Recently, our research group has screened a common neutralizing mono- clonal antibody named 8H5, which can neutralize almost all H5 subtype AIV ever isolated so far. Obvi- ously, this monoclonal antibody would benefit for research and development of the universal AIV vac- cine and design of the drug against H5N1 AIV in high mutation rate. In this study, the homology mod- eling was applied to generate the 3D structure of 8H5 Fab fragment, and 'canonical structure' method was used to define the specified loop conformation of CDR regions. The model was subjected to en- ergy minimization in cvff force field with Discovery module in Insight II program. The resulting model has correct stereochemistry as gauged from the Ramachandran plot calculation and good 3D-structure compatibility as assessed by interaction energy analysis, solvent accessible surface (SAS) analysis, and Profiles-3D approach. Furthermore, the 8H5 Fab model was subjected to docking with three H5 subtype hemagglutinin (HA) structures deposited in PDB (ID No: 1jsm, 2ibx and 2fk0) respectively. The result indicates that the three docked complexes share a common binding interface, but differ in bind- ing angle related with HA structure similarity between viral subtypes. In the light of the three HA inter- faces with structural homology analysis, the common neutralizing epitope on HA recognized by 8H5 consists of 9 incontinuous amino acid residues: Asp68, Asn72, Glu112, Lys113, Ile114, Pro118, Ser120, Tyr137, Tyr252 (numbered as for 1jsm sequence). The primary purpose of the present work is to provide some insight into structure and binding details of a common neutralizing epitope of H5N1 AIV, thereby aiding in the structure-based design of universal AIV vaccines and anti-virus therapeutic drugs. | YAN YuanQing LI ShaoWei YANG ChunYan LUO WenXin WANG MingQiao CHEN YiXin LUO HaiFeng wu Ting ZHANG Jun XIA NingShao | 2008 | Chinese Science Bulletin2008，53，6： | 2 |
| 4 | 分子对接预测H5亚型禽流感病毒的广谱中和表位显示文摘H5N1禽流感病毒已经在亚洲、欧洲和非洲广泛传播,造成了巨大损失.最近我们鉴定出一株对多种来源的H5N1代表株均有良好中和活性的、识别H5亚型血凝素(hemagglutinin,HA)的广谱单克隆抗体8H5,它对寻找克服禽流感高变性的广谱治疗性抗体、疫苗和药物具有重要价值.本研究应用分子模拟技术,采用'典范结构'方法对8H5抗体Fab片段进行结构模建,并通过能量分析、SAS值分析、'拉曼强传图'检验、profile-3D分析等理论验证,获得较为合理的8H5Fab的三维空间结构.8H5Fab与3种HA蛋白晶体结构的分子对接结果表明,8H5抗体与HA蛋白的作用模式与HA宿主来源无关,但与HA结构的亚型相似性相关.综合抗原同源比对结果,推测8H5抗体识别的广谱中和表位是由HA上的Asp68,Asn72,Glu112,Lys113,Ile114,Pro118,Ser120,Tyr137,Tyr252不连续氨基酸残基组成的构象表位.这一模型将为H5亚型禽流感病毒广谱疫苗和治疗性药物的分子设计提供依据。 | 颜渊清 李少伟 杨春燕 罗文新 王明桥 陈毅歆 罗海峰 吴婷 张军 夏宁邵 | 2008 | 科学通报2008，53，2： | 1 |
| 5 | 禽流感病毒H5N1血凝素基因适应性进化过程中的关键位点突变规律研究显示文摘目的:寻找导致禽流感病毒H5N1血凝素(HA)适应性进化的关键突变,建立氨基酸突变评价体系,对突变作用进行评估,印证它们与病毒适应性进化的关联性。方法:计算株频率和枝频率,寻找标记分枝,向根结点回溯寻找HA进化路径上的氨基酸突变。计算各突变位点氨基酸的频率变化、有效变换及高频次突变,基于以上几个因素建立突变评价体系。结果:建立了大规模自动化寻找突变的方法,计算得到HA进化过程中的氨基酸突变435个,通过氨基酸频率图表分析这些突变可以很好地反映病毒适应性进化过程,其中79个突变是有效变换,发生的位点为正选择位点,且多数位点落在HA抗原表位上;29个突变是高频次突变,其中多数也为有效变换,因而与病毒适应性进化密切相关。结论:大规模自动化寻找突变的方法可靠,建立的突变评价体系准确性高,找到的关键突变及位点对实验有很好的指导意义。 | 彭小川 靳远 胡明达 周江林 周静 岳俊杰 任洪广 梁龙 | 2019 | 生物技术通讯2019，30，1： | 0 |
| 6 | 格尔德霉素体内抑制高致病性禽流感病毒H5N1增殖显示文摘为了评价Hsp90抑制剂——格尔德霉素体内抗流感病毒的效果,利用高致病性禽流感病毒H5N1鼠适应株感染小鼠,分析格尔德霉素对流感病毒H5N1感染小鼠的死亡保护率以及不同时相肺部病毒负载量的影响.本实验用乙醚麻醉小鼠,流感病毒H5N1滴鼻感染C57BL/6小鼠,于感染后2h腹腔注射格尔德霉素,观察小鼠死亡保护率、体重变化及Real-time PCR检测小鼠肺部病毒负载量.生存分析结果显示格尔德霉素治疗组(80%)与对照组(3%)及奥司他韦治疗组(53%)相比极显著(P<0.01)地延长了流感病毒感染小鼠存活率及存活时间,且平均体重丢失也少于对照组及奥司他韦治疗组;Real-time PCR分析显示格尔德霉素极显著(P<0.01)地抑制了流感病毒H5N1的复制,与奥司他韦治疗组无显著性差异(P>0.05).上述实验结果显示格尔德霉素对流感病毒H5N1感染的小鼠提供了很好的保护作用,且显著抑制了流感病毒H5N1的增殖,可能作为一种新的、高效的抗流感病毒备选药物. | 刘朋朋 胡奕 赵宝华 仲飞 何宏轩 | 2013 | 科学通报2013，58，11： | 0 |
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