中国H3N2亚型人流感病毒神经氨酸酶基因的分子进化研究

发布时间：2018-01-22 23:30

本文关键词： 流感 H3N2亚型神经氨酸酶进化变异　出处：《湖南农业大学》2007年硕士论文　论文类型：学位论文

【摘要】： 为了了解中国大陆流行的H3N2亚型人流感病毒的NA基因变异特征与规律、进化趋势和毒株对NA抑制剂药物的耐药情况，本研究按一定原则选取了1968～2005年间国家流感中心保存的585株H3N2亚型人流感病毒毒株，通过对其NA基因的序列测定，采用生物信息学工具对序列进行分析，得出以下结论： (1)我国历年来NA基因的进化路径主要是以一主要的进化主干伴随着多侧支的方式进化，序列的差距与年代大体成正比，NA的进化不存在明显的地域特征，，流感病毒株新变种的出现，在时间上无周期性。 (2)疫苗株在我国历年来NA的核苷酸和氨基酸进化树上存在明显的滞后现象。 (3) NA氨基酸和核苷酸各年间的进化率呈折叠形，流行高峰年份的毒株进化率位于峰点。从整体上看，氨基酸的进化速度大于核苷酸，抗原决定簇位点的进化最快，茎部与跨膜区次之，但是流行高峰期，具体到哪些位点会发生变异，没有规律可言。 (4) NA历年来只有48％的氨基酸位点出现变异，大部分位点保守且没有氨基酸的缺失与插入。7个抗原决定簇变异率均不相同，197～199位变异率最高，是最重要的抗原位点，而153位变异率最低；所有位点中197位变异最快。NA的酶活性位点高度保守，且我国1968～2005年间在基因水平上没有监测到耐药株。二硫键和糖基化位点相对保守，糖基化位点突然出现与消失可能是引起流感流行的原因之一。通过分析还发现143、267和385位氨基酸的变异率高于抗原决定簇位点，但具体生物学意义不清楚。 (5)本研究是首次对中国大陆历年来H3N2亚型人流感病毒NA基因进行分子进化分析，首次阐明了我国H3N2亚型人流感病毒NA基因的特性和进化情况。这为以后我国大陆的流感监测与防治工作提供了基础理论依据以及为NA抑制剂药物的使用提供指导作用。
[Abstract]:In order to understand the characteristics and regularity of na gene variation, evolutionary trend and drug resistance of H3N2 subtype human influenza virus (H3N2) in mainland China. In this study, 585 strains of H3N2 subtype human influenza virus were selected from the National Influenza Center during 19682005, and their na gene sequences were sequenced. Using bioinformatics tools to analyze the sequence, the following conclusions are drawn: 1) the evolution path of na gene in China over the years is mainly based on a main evolutionary trunk accompanied by multiple branches, and the sequence gap is approximately proportional to the age. The evolution of na has no obvious regional characteristics, and the emergence of new strains of influenza virus has no periodicity in time. (2) the vaccine strain has obvious lag phenomenon on the nucleotide and amino acid evolution tree of na in China over the years. 3) the evolution rate of na amino acids and nucleotides was folded in each year, and the evolution rate of strains in peak epidemic years was at the peak point. On the whole, the evolution rate of amino acids was faster than that of nucleotides. The evolution of antigen-determinant loci is the fastest followed by stem and transmembrane regions but there is no rule to describe which loci will mutate in the peak period of epidemic. (4) only 48% amino acid loci of na have mutated over the years, most of them are conserved and have no amino acid deletion or insertion. The variation rates of the seven antigenic determinants are different. The variation rate of 199 was the highest and the most important antigenic site, while the 153-position mutation rate was the lowest. The enzyme activity sites at the 197th locus with the fastest variation were highly conserved, and no drug-resistant strains were detected at the gene level in China during 19682005. The disulfide bond and glycosylation sites were relatively conserved. The sudden appearance and disappearance of glycosylation sites may be one of the causes of influenza epidemic. It was also found that the mutation rate of amino acids at the 143,267 and 385th sites was higher than that of the antigenic determinant loci. But the specific biological significance is not clear. This study is the first time to analyze the na gene of H3N2 subtype human influenza virus in mainland China. The characteristics and evolution of na gene of H3N2 subtype human influenza virus in China were first elucidated, which provided the basic theoretical basis for the surveillance and prevention of influenza in mainland China, and provided the basis for the development of na inhibitor drugs. To provide guidance.
【学位授予单位】：湖南农业大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R373

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