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[2014 - 2017年贵州省甲型H7N9禽流感病毒血凝素和神经氨酸酶的遗传特征]

[Genetic characteristics of hemagglutinin and neuraminidase of avian influenza A (H7N9) virus in Guizhou province, 2014-2017].

作者信息

Wan Y H, Zhuang L, Zheng Q N, Ren L J, Fu L, Jiang W J, Tang G P, Zhang D Z, Li S J

机构信息

Guizhou Provincial Center for Disease Control and Prevention, Guiyang 550004, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2018 Nov 10;39(11):1465-1471. doi: 10.3760/cma.j.issn.0254-6450.2018.11.009.

Abstract

To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province. RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package. Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue "QISNT" in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains. HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.

摘要

为了解贵州省甲型H7N9流感病毒血凝素(HA)和神经氨酸酶(NA)分子特征及疾病风险。对2014 - 2017年贵州省18例人感染H7N9病毒病例及6份环境拭子中分离的H7N9病毒株的HA和NA基因进行RNA提取及测序,然后运用一系列生物信息学软件包对病毒的变异及遗传进化进行分析。HA和NA基因同源性分析显示,2014 - 2015年检测到的2株病毒与世界卫生组织推荐的疫苗株A/Shanghai/2/2013和A/Anhui/1/2013的相似性分别为98.8% - 99.2%和99.2%;2016年检测到的2株病毒及2017年检测到的14株病毒与疫苗株A/Hunan/02650/2016的相似性分别为98.2% - 99.3%和97.6% - 98.8%;2017年检测到的其他6株病毒与毒株A/Guangdong/17SF003/2016的相似性分别为99.1% - 99.4%和98.9% - 99.3%。系统进化分析表明,所有毒株均直接在长江三角洲进化分支中演化,但源自不同的小分支。在24株HA蛋白裂解位点序列中有6株发现PEVPKRKRTAR↓GLF,表明具有高致病性禽流感病毒特征。在HA中发现受体结合位点的A134V、G186V和Q226L突变。所有毒株NA蛋白均有5个氨基酸残基“QISNT”的柄部缺失,毒株A/Guizhou-Danzhai/18980/2017发生耐药性突变R294K。此外,24株中有9株NA发现潜在糖基化基序突变NCS42NCT。2014 - 2017年贵州省甲型H7N9禽流感病毒HA和NA基因呈现遗传分化。关键位点的突变可能增强病毒毒力,人类对其更易感染。因此,感染风险在增加。

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