本文關(guān)鍵詞： 流感 H3N2亞型 神經(jīng)氨酸酶 進(jìn)化 變異　出處：《湖南農(nóng)業(yè)大學(xué)》2007年碩士論文　論文類型：學(xué)位論文

【摘要】： 為了了解中國(guó)大陸流行的H3N2亞型人流感病毒的NA基因變異特征與規(guī)律、進(jìn)化趨勢(shì)和毒株對(duì)NA抑制劑藥物的耐藥情況，本研究按一定原則選取了1968～2005年間國(guó)家流感中心保存的585株H3N2亞型人流感病毒毒株，通過對(duì)其NA基因的序列測(cè)定，采用生物信息學(xué)工具對(duì)序列進(jìn)行分析，得出以下結(jié)論： (1)我國(guó)歷年來NA基因的進(jìn)化路徑主要是以一主要的進(jìn)化主干伴隨著多側(cè)支的方式進(jìn)化，序列的差距與年代大體成正比，NA的進(jìn)化不存在明顯的地域特征，，流感病毒株新變種的出現(xiàn)，在時(shí)間上無周期性。 (2)疫苗株在我國(guó)歷年來NA的核苷酸和氨基酸進(jìn)化樹上存在明顯的滯后現(xiàn)象。 (3) NA氨基酸和核苷酸各年間的進(jìn)化率呈折疊形，流行高峰年份的毒株進(jìn)化率位于峰點(diǎn)。從整體上看，氨基酸的進(jìn)化速度大于核苷酸，抗原決定簇位點(diǎn)的進(jìn)化最快，莖部與跨膜區(qū)次之，但是流行高峰期，具體到哪些位點(diǎn)會(huì)發(fā)生變異，沒有規(guī)律可言。 (4) NA歷年來只有48％的氨基酸位點(diǎn)出現(xiàn)變異，大部分位點(diǎn)保守且沒有氨基酸的缺失與插入。7個(gè)抗原決定簇變異率均不相同，197～199位變異率最高，是最重要的抗原位點(diǎn)，而153位變異率最低；所有位點(diǎn)中197位變異最快。NA的酶活性位點(diǎn)高度保守，且我國(guó)1968～2005年間在基因水平上沒有監(jiān)測(cè)到耐藥株。二硫鍵和糖基化位點(diǎn)相對(duì)保守，糖基化位點(diǎn)突然出現(xiàn)與消失可能是引起流感流行的原因之一。通過分析還發(fā)現(xiàn)143、267和385位氨基酸的變異率高于抗原決定簇位點(diǎn)，但具體生物學(xué)意義不清楚。 (5)本研究是首次對(duì)中國(guó)大陸歷年來H3N2亞型人流感病毒NA基因進(jìn)行分子進(jìn)化分析，首次闡明了我國(guó)H3N2亞型人流感病毒NA基因的特性和進(jìn)化情況。這為以后我國(guó)大陸的流感監(jiān)測(cè)與防治工作提供了基礎(chǔ)理論依據(jù)以及為NA抑制劑藥物的使用提供指導(dǎo)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.
【學(xué)位授予單位】：湖南農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R373

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 趙斐斐;1998-2009年浙江省流感主要流行株H3N2的全基因組特性研究[D];寧波大學(xué);2011年

本文編號(hào)：1456031