长春地区由柯萨奇病毒A6型引起的手足口病分子生物学及致病特性的研究

发布时间：2018-01-19 19:41

本文关键词： 柯萨奇病毒A6型病毒载量乳鼠模型死亡率重组　出处：《吉林大学》2017年硕士论文　论文类型：学位论文

【摘要】：手足口病(hand-foot-mouth disease,HFMD)自2008年以来在世界各地都有爆发,在2013年中国多地由CV-A6引发了大范围的HFMD流行。目前对CV-A6的研究仅见病例报道及流行病学分析,而其遗传特征和致病特性等还未见报道。本研究中,我们报道了2013年在长春地区手足口病患者中分离出的39个CV-A6-CC株的部分VP1区序列,且获得了其中4株具有代表性的CV-A6-CC株的全基因组序列,并登陆Genbank数据库。部分VP1区的系统进化树分析表明,CV-A6-CC株与世界其他地方来源的CV-A6一样,分布在3个大支里。CV-A6-CC株全序列与世界其他地区来源的CV-A6做系统进化树分析,结果表明CV-A6-CC株可能是来源于CV-A6原型株Gdula与CV-A6-日本株和上海株的重组。重组分析结果表明,CV-A6-CC株可能是Gdula株和CV-A4的原型株或其他类似于CV-A4的病毒株重组而来,其重组模式与从中国其他地区来源的CV-A6株不太一致。进一步的,我们建立了致死性新生ICR乳鼠模型,用4种病毒株分别免疫乳鼠,观察并记录免疫后乳鼠出现的临床症状评分及生存率;此外,我们还测定了致病乳鼠9种组织及血液中的病毒载量,并且进行了病理学分析,以此来研究CV-A6病毒对新生乳鼠的致病作用,结果表明,不同的CV-A6-CC株病毒在乳鼠模型中具有不同的致病能力,根据其致病特性可以将CV-A6-CC株分为致死株(CC046、CC097和CC099)及非致死株(CC098)。我们的研究第一次报道了引起手足口病的CV-A6病毒可以分为致死株和非致死株,这将为我们进一步的研究CV-A6病毒的致病分子机制研究奠定基础。
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.5

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