2011-2012年江浙部分地区H9N2 AIV分子流行病学调查

发布时间：2018-02-07 09:53

本文关键词： 禽流感 H9N2 基因序列抗原性交叉免疫保护　出处：《南京农业大学》2015年硕士论文　论文类型：学位论文

【摘要】：H9N2亚型禽流感自1994年首次在我国广东地区发生以来,H9N2亚型禽流感广泛流行于我国鸡群中。随着禽流感病毒抗原漂移和抗原突变的日积月累,使得禽类与人类之间的种属屏障正在减弱或消失,对人类的公共卫生安全存在巨大威胁。持续了解流感病毒的遗传变异、不断地评价病毒的抗原转变,对于及时捕捉到可引起人类流感大流行的毒株,并研制有效疫苗具有非常重要的意义。为了解和监测近年来H9N2亚型禽流感病毒的分子演化情况,选取2011-2012年所分离的14株H9N2亚型禽流感病毒,进行全基因组的序列测定,应用生物软件分析基因序列和变异情况,揭示H9N2亚型禽流感病毒的流行规律。本研究结果表明,2011-2012年江浙部分地区分离的14株H9N2亚型禽流感病毒均具有低致病性禽流感病毒的分子特征。HA基因属于Y280-like亚分支,糖基化位点的缺失可能会引起病毒毒力的变化,大多数分离株的234位受体结合位点为L,呈现出与人流感受体结合的特性,表明近些年的H9N2亚型禽流感病毒已具备使哺乳动物致病的能力。NA基因属于Y280-like亚分支,分离株全部存在颈部缺失的现象。PA、PB1、NP基因全部属于SH/F/98-like亚分支,与经典毒株相比,多处位点氨基酸发生了变异。M基因属于Gl-like亚分支,均不具有对金刚烷胺类药物的抗药性。NS基因则分属于两个亚分支SH/F98-like和Y439-like,均具有能够逃避干扰素IFN和肿瘤坏死因子TNF-a的抗病毒性,氨基酸也存在变异现象,两个亚群的个别位点氨基酸出现明显的差异。PB2基因则完全独立形成一个新的亚分支。14株H9N2毒株的所有内部基因的位点氨基酸变异现象与H7N9毒株相一致。对近几年的H9N2亚型禽流感病毒监测表明,病毒的抗原性发生了比较显著的变化,有的是在疫苗的免疫压力下出现了免疫逃避现象,导致免疫失败的发生。本研究对14株H9N2亚型禽流感病毒的交叉免疫保护作用分析,结果表明,JS1102、ZJ1107、JS1109、JS1204的抗原性比较接近,HI抗体效价平均为81og2,4株病毒之间的交互HI值差异在3 log2左右,抗原相关值位于0.8～1之间;未免疫而攻毒的对照组5d时排毒的比例分别为5/5、5/5、4/5、4/5,免疫组在攻毒后5d时拭子样品病毒分离均为阴性,毒株之间具有较好的免疫原性,彼此能够产生很好的免疫保护效果。
[Abstract]:H9N2 subtype avian influenza (H9N2) has been widely prevalent in Chinese chickens since its first occurrence in Guangdong in 1994. With the accumulation of antigen drift and antigen mutation of avian influenza virus, H9N2 subtype avian influenza virus (H9N2) subtype avian influenza virus (H9N2) has been widely prevalent in Chinese chickens since 1994. Making the species barrier between birds and humans weakening or disappearing, posing a huge threat to human public health and safety. Keeping an understanding of the genetic variation of influenza viruses, constantly evaluating the antigenic changes of viruses, In order to understand and monitor the molecular evolution of H9N2 subtype avian influenza virus in recent years, it is of great significance to catch the virus that can cause the human influenza pandemic and to develop an effective vaccine. Fourteen strains of H9N2 subtype avian influenza virus isolated from 2011-2012 were selected and sequenced for the whole genome, and the gene sequence and variation were analyzed by biological software. The results showed that 14 strains of H9N2 subtype avian influenza virus isolated from Jiangsu and Zhejiang provinces from 2011 to 2012 all had the molecular characteristics of low pathogenic avian influenza virus. The HA gene belonged to Y280-like subbranch. The absence of glycosylation sites may lead to changes in virulence of the virus. The 234-site receptor binding site of most isolates is L, showing the characteristics of binding to human influenza receptors. These results indicate that the H9N2 subtype avian influenza virus has the ability to cause disease in mammals. Na gene belongs to Y280-like subbranch, and all the isolates have neck deletion. The NP gene belongs to the subbranch of SH/F/98-like, compared with the classical strain. The amino acids at many sites are mutated. M gene belongs to the subbranch of Gl-like. The NS gene belonged to two subbranches of SH/F98-like and Y439-like. Both of them had antiviral resistance to interferon IFN and tumor necrosis factor TNF-a, and the amino acids were also mutated. The amino acids of individual sites in the two subgroups were obviously different. PB2 gene was completely independent to form a new subbranch. 14 strains of H9N2 strain had the same amino acid variation in all internal genes as those of H7N9 strain. In recent years, the variation of amino acids in all internal genes of H9N2 strain was consistent with that of H7N9 strain. The H9N2 subtype avian influenza virus surveillance showed that, The antigenicity of the virus changed significantly, some of which appeared immune escape phenomenon under the immune pressure of the vaccine, which resulted in the immune failure. This study analyzed the cross-immunological protection of 14 strains of H9N2 subtype avian influenza virus. The results showed that the antigenicity of JS1102ZJ1107J1109 / JS1204 was close to the average HI antibody titer of 81og2 strain. The difference of HI value between the two strains was about 3 log2, and the antigenic correlation value was between 0.8 log2. The proportion of detoxification in the unimmunized control group was 5 / 5 / 5 / 5 / 5 / 5 / 5 / 5 / 5 respectively. The virus isolated from the swabs samples in the immunized group was negative at the 5th day after the attack, and there was good immunogenicity among the strains, which could produce a good immune protection effect.
【学位授予单位】：南京农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S855.3

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