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長春地區(qū)由柯薩奇病毒A6型引起的手足口病分子生物學及致病特性的研究

發(fā)布時間:2018-01-19 19:41

  本文關(guān)鍵詞: 柯薩奇病毒A6型 病毒載量 乳鼠模型 死亡率 重組 出處:《吉林大學》2017年碩士論文 論文類型:學位論文


【摘要】:手足口病(hand-foot-mouth disease,HFMD)自2008年以來在世界各地都有爆發(fā),在2013年中國多地由CV-A6引發(fā)了大范圍的HFMD流行。目前對CV-A6的研究僅見病例報道及流行病學分析,而其遺傳特征和致病特性等還未見報道。本研究中,我們報道了2013年在長春地區(qū)手足口病患者中分離出的39個CV-A6-CC株的部分VP1區(qū)序列,且獲得了其中4株具有代表性的CV-A6-CC株的全基因組序列,并登陸Genbank數(shù)據(jù)庫。部分VP1區(qū)的系統(tǒng)進化樹分析表明,CV-A6-CC株與世界其他地方來源的CV-A6一樣,分布在3個大支里。CV-A6-CC株全序列與世界其他地區(qū)來源的CV-A6做系統(tǒng)進化樹分析,結(jié)果表明CV-A6-CC株可能是來源于CV-A6原型株Gdula與CV-A6-日本株和上海株的重組。重組分析結(jié)果表明,CV-A6-CC株可能是Gdula株和CV-A4的原型株或其他類似于CV-A4的病毒株重組而來,其重組模式與從中國其他地區(qū)來源的CV-A6株不太一致。進一步的,我們建立了致死性新生ICR乳鼠模型,用4種病毒株分別免疫乳鼠,觀察并記錄免疫后乳鼠出現(xiàn)的臨床癥狀評分及生存率;此外,我們還測定了致病乳鼠9種組織及血液中的病毒載量,并且進行了病理學分析,以此來研究CV-A6病毒對新生乳鼠的致病作用,結(jié)果表明,不同的CV-A6-CC株病毒在乳鼠模型中具有不同的致病能力,根據(jù)其致病特性可以將CV-A6-CC株分為致死株(CC046、CC097和CC099)及非致死株(CC098)。我們的研究第一次報道了引起手足口病的CV-A6病毒可以分為致死株和非致死株,這將為我們進一步的研究CV-A6病毒的致病分子機制研究奠定基礎(chǔ)。
[Abstract]:Hand-foot-mouth disease (HFMD) has been occurring around the world since 2008. In 2013, CV-A6 caused a widespread HFMD epidemic in China. So far, only case reports and epidemiological analysis have been reported on CV-A6. But its genetic characteristics and pathogenic characteristics have not been reported. In this study. In 2013, we reported the partial VP1 sequence of 39 CV-A6-CC strains isolated from patients with HFMD in Changchun area. The whole genome sequences of 4 representative CV-A6-CC strains were obtained and entered into the Genbank database. Phylogenetic tree analysis of some VP1 regions showed that. CV-A6-CC strains are the same as CV-A6 from other parts of the world. The whole sequence of CV-A6-CC strain and CV-A6 from other parts of the world were analyzed by phylogenetic tree. The results showed that the CV-A6-CC strain probably originated from the recombination of CV-A6 prototype strain Gdula, CV-A6- Japanese strain and Shanghai strain. CV-A6-CC strain may be the recombination of Gdula strain and CV-A4 prototype strain or other similar to CV-A4 virus strain. The recombinant model was not identical with the CV-A6 strain from other regions of China. Furthermore, we established a fatal neonatal ICR model and immunized the newborn mice with four different strains of virus. The clinical symptom score and survival rate were observed and recorded. In addition, we also measured the viral load in 9 tissues and blood of the disease-causing neonatal mice, and carried out pathological analysis to study the pathogenicity of CV-A6 virus on newborn neonatal mice. Different CV-A6-CC strains have different pathogenicity in neonatal rat model. According to their pathogenicity, CV-A6-CC strain can be divided into lethal strain CC046. CC097 and CC099) and non-lethal strain CC0981.We reported for the first time that the CV-A6 virus causing HFMD could be divided into lethal strain and non-lethal strain. This will lay a foundation for our further study on the pathogenesis of CV-A6 virus.
【學位授予單位】:吉林大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R512.5

【參考文獻】

相關(guān)期刊論文 前2條

1 陳煒;翁育偉;何文祥;張擁軍;楊秀惠;黃萌;謝劍鋒;王金章;鄭奎城;嚴延生;;2011~2013年福建省手足口病相關(guān)病原柯薩奇病毒A組6型的分子流行病學研究[J];病毒學報;2014年06期

2 ;Surveillance of Hand,Foot,and Mouth Disease in Mainland China (2008-2009)[J];Biomedical and Environmental Sciences;2011年04期

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