2010~2015年福建省乙型流感流行状况与病毒基因特征研究

发布时间：2018-03-25 03:19

本文选题：乙型流感　切入点：流行状况　出处：《福建医科大学》2016年硕士论文

【摘要】：目的:本研究通过对福建省2010~2015年乙型流感的流行状况进行分析,同时研究乙型流感毒株血凝素和神经氨酸酶的分子变异特征,探讨我省近6年乙型流感病毒的变异情况,为乙型流感的预防控制和疫苗的研制提供科学的依据。方法:收集整理2010~2015年各哨点医院流感监测数据,应用EXCEL和SPSS软件进行统计分析。利用生物信息学软件对所测乙型流感毒株的HA和NA序列进行拼接、比对,分析毒株HA和NA蛋白氨基酸位点的变化情况。结果:1、2009年甲型H1N1流行过后,我省乙型流感、甲型H1N1流感和季节性H3N2流感流行优势交替出现。2、乙型流感监测结果表明:乙型流感主要在冬春季节较为活跃,不同年龄组和地区阳性率差异有统计学意义,以5~24岁组为易感人群,沿海地区阳性率高于非沿海地区。3、氨基酸同源性分析显示,本次研究的乙型流感病毒株与同期的疫苗株相比仍保持较高的同源性。4、遗传进化分析显示,2013~2014年我省出现BY-HA/BV-NA重组的乙型流感病毒。5、HA分子特性分析显示,Yamagata系毒株之间在HA基因上共有45个位点的氨基酸存在差异,且随时间的推移变异位点逐渐增多,尤以2011年、2014年和2015年变异较为明显。与Yamagata系毒株相比,Victoria系毒株HA基因的变异较小,且没有明显随时间累积的趋势。6、NA分子特性分析显示,非重配Yamagata系毒株在NA基因上共有28个位点的氨基酸存在差异,其中有10个位点发生反复回变。Victoria系毒株在NA基因上共有31个位点的氨基酸存在差异,其中8个位点为回复突变点,18个位点为易变点。重配的Yamagata毒株在NA基因上与两个种系疫苗株均差异明显。7、WHO推荐的Yamagata系流感疫苗株相对当前流行的毒株存在明显的滞后现象。2010年和2015年两个年份WHO推荐的Yamagata系疫苗株对福建省的乙型流感保护效果不佳,其余年份的Yamagata系疫苗株对人群保护作用尚可,而Victoria系疫苗株仍具有较好的保护效果。8、本次研究发现NA基因的酶活性中心和周围的相关位点氨基酸仍保持高度保守,未发现耐药相关突变位点。9、糖基化分析显示,Yamagata系毒株在HA蛋白的196位上增加一个糖基化位点,这个位点位于HA蛋白抗原决定簇区的190环,同时也是受体结合位点,可能会影响抗体对病毒的识别和结合,部分毒株在NA蛋白上的463位增加一个糖基化位点,且该糖基化位点在不同年份中反复丢失和恢复,这是否影响病毒的增殖和适应性等,还有待进一步的研究。结论:流感监测结合病毒基因特征分析可以为流感的防控提供重要依据,本次研究发现基因重配和抗原漂移是我省乙型流感病毒进化的主要方式。随着时间的推移,乙型流感病毒已经逐渐发生变异,部分年份的毒株与疫苗株的匹配性不佳,出现了41株抗原漂移株。未来福建省的乙型流感仍将会以两个种系交替流行。
[Abstract]:Objective: to study the molecular variation of hemagglutinin and neuraminidase of influenza B strain from 2010 to 2015 in Fujian Province, and to explore the variation of influenza B virus in recent 6 years in Fujian Province. To provide scientific basis for the prevention and control of influenza B and the development of vaccine. Methods: collecting and sorting out the surveillance data of influenza in sentinel hospitals from 2010 to 2015. The HA and na sequences of influenza B strain were spliced and compared with each other by using EXCEL and SPSS software. The changes of amino acid loci of HA and na proteins were analyzed. Results: after the epidemic of A H1N1 in 2009, influenza B was detected in our province. The results of influenza B surveillance showed that influenza B was mainly active in winter and spring, and the positive rate of influenza B in different age groups and regions was significantly different. The positive rate in coastal area was higher than that in non-coastal area. The amino acid homology analysis showed that the positive rate was higher than that in non-coastal area. Compared with the vaccine strain of the same period, the influenza B virus strain in this study still maintained a high homology .4.The genetic evolution analysis showed that the BY-HA/BV-NA recombined influenza B virus. 5AHA molecular characteristic analysis showed that the virus strain of Yamagata strain was among the strains of BY-HA/BV-NA recombination in our province from 2013 to 2014. There were 45 amino acid differences in HA gene. The variation sites of HA gene were increased gradually with time, especially in 2011, 2014 and 2015. Compared with Yamagata strain, the variation of HA gene was small, and there was no obvious trend of accumulation over time. There were 28 amino acid differences in the na gene of non-reassorted Yamagata strains, among which 10 of them had repeated reversion. There were 31 amino acids differences in na gene of the non-reassorted Yamagata strains. Among them, 8 loci are reverse-mutation sites and 18 loci are variable sites. There are significant differences in na gene between the reassorted Yamagata strains and the two strains of vaccine strains. 70.The Yamagata influenza vaccine strains recommended by WHO are significantly different from those of the current epidemic strains. Lag phenomenon. The Yamagata strain recommended by WHO in 2010 and 2015 is not effective for the protection of influenza B in Fujian Province. In the other years, the Yamagata vaccine strain had a good protective effect on the population, while the Victoria strain vaccine strain still had a good protective effect. This study found that the enzyme active center of na gene and the amino acids of the related sites around the na gene remained highly conserved. No drug-resistance related mutation locus was found. Glycosylation analysis showed that Yamagata strain added a glycosylation site to the 196 position of HA protein, which is located in the 190 ring of the antigen determinant of HA protein and is also a receptor binding site. It may affect the recognition and binding of the antibody to the virus. Some strains have added a glycosylation site to the 463 position of na protein, and the glycosylation site has been repeatedly lost and recovered in different years, whether this affects the proliferation and adaptability of the virus, etc. Conclusion: influenza surveillance combined with virus gene analysis can provide an important basis for the prevention and control of influenza. This study found that gene rematch and antigen drift are the main ways of influenza B virus evolution in our province. With the passage of time, influenza B virus has gradually mutated, and in some years the virus strains do not match well with the vaccine strains. There are 41 antigenic drift strains. In the future, influenza B in Fujian Province will continue to spread alternately between two strains.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R511.7

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