本文選題：乙型流感　切入點(diǎn)：流行狀況　出處：《福建醫(yī)科大學(xué)》2016年碩士論文

【摘要】：目的:本研究通過對(duì)福建省2010~2015年乙型流感的流行狀況進(jìn)行分析,同時(shí)研究乙型流感毒株血凝素和神經(jīng)氨酸酶的分子變異特征,探討我省近6年乙型流感病毒的變異情況,為乙型流感的預(yù)防控制和疫苗的研制提供科學(xué)的依據(jù)。方法:收集整理2010~2015年各哨點(diǎn)醫(yī)院流感監(jiān)測(cè)數(shù)據(jù),應(yīng)用EXCEL和SPSS軟件進(jìn)行統(tǒng)計(jì)分析。利用生物信息學(xué)軟件對(duì)所測(cè)乙型流感毒株的HA和NA序列進(jìn)行拼接、比對(duì),分析毒株HA和NA蛋白氨基酸位點(diǎn)的變化情況。結(jié)果:1、2009年甲型H1N1流行過后,我省乙型流感、甲型H1N1流感和季節(jié)性H3N2流感流行優(yōu)勢(shì)交替出現(xiàn)。2、乙型流感監(jiān)測(cè)結(jié)果表明:乙型流感主要在冬春季節(jié)較為活躍,不同年齡組和地區(qū)陽性率差異有統(tǒng)計(jì)學(xué)意義,以5~24歲組為易感人群,沿海地區(qū)陽性率高于非沿海地區(qū)。3、氨基酸同源性分析顯示,本次研究的乙型流感病毒株與同期的疫苗株相比仍保持較高的同源性。4、遺傳進(jìn)化分析顯示,2013~2014年我省出現(xiàn)BY-HA/BV-NA重組的乙型流感病毒。5、HA分子特性分析顯示,Yamagata系毒株之間在HA基因上共有45個(gè)位點(diǎn)的氨基酸存在差異,且隨時(shí)間的推移變異位點(diǎn)逐漸增多,尤以2011年、2014年和2015年變異較為明顯。與Yamagata系毒株相比,Victoria系毒株HA基因的變異較小,且沒有明顯隨時(shí)間累積的趨勢(shì)。6、NA分子特性分析顯示,非重配Yamagata系毒株在NA基因上共有28個(gè)位點(diǎn)的氨基酸存在差異,其中有10個(gè)位點(diǎn)發(fā)生反復(fù)回變。Victoria系毒株在NA基因上共有31個(gè)位點(diǎn)的氨基酸存在差異,其中8個(gè)位點(diǎn)為回復(fù)突變點(diǎn),18個(gè)位點(diǎn)為易變點(diǎn)。重配的Yamagata毒株在NA基因上與兩個(gè)種系疫苗株均差異明顯。7、WHO推薦的Yamagata系流感疫苗株相對(duì)當(dāng)前流行的毒株存在明顯的滯后現(xiàn)象。2010年和2015年兩個(gè)年份WHO推薦的Yamagata系疫苗株對(duì)福建省的乙型流感保護(hù)效果不佳,其余年份的Yamagata系疫苗株對(duì)人群保護(hù)作用尚可,而Victoria系疫苗株仍具有較好的保護(hù)效果。8、本次研究發(fā)現(xiàn)NA基因的酶活性中心和周圍的相關(guān)位點(diǎn)氨基酸仍保持高度保守,未發(fā)現(xiàn)耐藥相關(guān)突變位點(diǎn)。9、糖基化分析顯示,Yamagata系毒株在HA蛋白的196位上增加一個(gè)糖基化位點(diǎn),這個(gè)位點(diǎn)位于HA蛋白抗原決定簇區(qū)的190環(huán),同時(shí)也是受體結(jié)合位點(diǎn),可能會(huì)影響抗體對(duì)病毒的識(shí)別和結(jié)合,部分毒株在NA蛋白上的463位增加一個(gè)糖基化位點(diǎn),且該糖基化位點(diǎn)在不同年份中反復(fù)丟失和恢復(fù),這是否影響病毒的增殖和適應(yīng)性等,還有待進(jìn)一步的研究。結(jié)論:流感監(jiān)測(cè)結(jié)合病毒基因特征分析可以為流感的防控提供重要依據(jù),本次研究發(fā)現(xiàn)基因重配和抗原漂移是我省乙型流感病毒進(jìn)化的主要方式。隨著時(shí)間的推移,乙型流感病毒已經(jīng)逐漸發(fā)生變異,部分年份的毒株與疫苗株的匹配性不佳,出現(xiàn)了41株抗原漂移株。未來福建省的乙型流感仍將會(huì)以兩個(gè)種系交替流行。
[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.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R511.7

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