S gene variations of hepatitis B virus in children with vaccination failure

Deng Haijun; Huang Yong; Long Quanxin; Huang Ailong

doi:10.13406/j.cnki.cyxb.000803

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S gene variations of hepatitis B virus in children with vaccination failure

更新时间：2024-01-17

- S gene variations of hepatitis B virus in children with vaccination failure
- Journal of Chongqing Medical University Vol. 41, Issue 1, Pages: 76-80(2016)
- 作者机构：
  
  1. 重庆医科大学感染性疾病分子生物学教育部重点实验室
  2. 重庆医科大学附属第二医院检验科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.000803
  CLC： R186.2
- Published：2016，
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[1]邓海君,黄勇,龙泉鑫,黄爱龙.重庆地区乙肝疫苗免疫无效儿童病毒基因组表面抗原区变异研究[J].重庆医科大学学报,2016,41(01):76-80.

Deng Haijun, Huang Yong, Long Quanxin, et al. S gene variations of hepatitis B virus in children with vaccination failure. [J]. Journal of Chongqing Medical University 41(1):76-80(2016)
[1]邓海君,黄勇,龙泉鑫,黄爱龙.重庆地区乙肝疫苗免疫无效儿童病毒基因组表面抗原区变异研究[J].重庆医科大学学报,2016,41(01):76-80. DOI： 10.13406/j.cnki.cyxb.000803.

Deng Haijun, Huang Yong, Long Quanxin, et al. S gene variations of hepatitis B virus in children with vaccination failure. [J]. Journal of Chongqing Medical University 41(1):76-80(2016) DOI： 10.13406/j.cnki.cyxb.000803.

摘要

目的 :探讨重庆地区乙型肝炎病毒（hepatitis B virus

HBV）疫苗免疫失败儿童患者体内病毒表面抗原（surface gene）基因主要亲水区（major hydrophilic region

MHR）及a决定簇变异情况。方法:收集乙型肝炎病毒疫苗免疫保护失败患儿及未接种疫苗的乙型肝炎病毒感染患儿血清样本

通过扩增HBV S基因并测序

与相应基因型的标准序列进行比对分析。结果:243例免疫保护失败患儿体内病毒a决定簇突变检出率明显高于20例未经疫苗免疫组患儿（31.7%vs.10.0%

P=0.044）;免疫失败组儿童体内病毒MHR突变率数值也高于未接种组儿童

在统计学上差异不显著（49.8%vs.30.0%

P=0.106）。在疫苗免疫失败儿童病例中

MHR和a决定簇突变发生与病毒低水平复制相关:突变组患儿DNA滴度均明显低于无突变组患儿（log106.9±1.8vs.log107.7±1.8

P=0.000;log107.1±1.6 vs.log107.6±1.9

P=0.000）。免疫失败儿童病例中

MHR突变组儿童谷丙转氨酶（alanine aminotransferase

ALT）数值也明显高于未突变组（67.1±58.8 vs.56.5±51.8

P=0.018）。在243例疫苗免疫保护失败儿童体内病毒MHR区域中共检出145个变异氨基酸

热点变异类型主要包括I110L（6例）、K122R（15例）、T126A（18例）、I126T（14例）、M133L（7例）、G145R（6例）及Y161F（12例）等。进一步分析各类型突变与临床表型间差异

发现含G145R及Y161F突变病例体内血清病毒DNA水平明显低于无突变组（log106.8±1.1 vs.log107.5±1.8

P=0.048;log105.0±2.6 vs.log107.3±1.8

P=0.000）。结论:疫苗免疫保护失败儿童病例体内病毒a决定簇及MHR具有较高的突变率

且该区段的突变与病毒较低的复制水平及及较高的ALT相关。

Abstract

Objective:To determine variations of ‘major hydrophilic region’(MHR)and ‘a determinant region’in S gene of hepatitis B virus(HBV)in children with vaccine immunized failure. Methods:Serum samples from HBV vaccine immunized failure child and non-immunized child were collected;HBV S gene was amplified

sequenced

and compared with the consensus sequence of different genotype HBV genomes. Results:Nucleotide mutation ratio of ‘a determinant region’in HBV patients with vaccine immunized failure was obviously higher than that of vaccine navie patients(31.7% vs. 10.0%

P=0.044). Vaccine immunized failure patients with mutation in MHR or a determinant had a obviously lower viral DNA loading compared with that of mutation free patients(MHR:log106.9±1.8 vs. log107.7±1.8

P=0.000;a determinant:log107.1±1.6 vs. log107.6±1.9

P=0.000). In addition

vaccine immunized failure patients with MHR mutation also had higher ALT value(67.1±58.8 vs. 56.5±51.8

P=0.018). Totally 145 amino acid variation types were detected in vaccine immunized failure patients

including several ‘hot mutations’ :I110L(6)

K122R(15)

T126A(18)

I126T(14)

M133L(7)

G145R(6)and Y161F(12).Patients with G145 R and Y161 F had obviously lower serum viral loading(log106.8±1.1 vs. log107.5±1.8

P=0.048;log105.0±2.6 vs. log107.3±1.8

P=0.000

respectively). Conclusion:In general

vaccine immunized failure children have a higher mutation rate in MHR region and a determinant region

which correlate with lower viral loading and higher ALT value.

关键词

乙型肝炎病毒疫苗保护失败儿童病例病毒变异

Keywords

hepatitis B virusvaccination failurechild patientsvirus variations

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Related Author

Lan Yukang

Qi Xiaoying

Gui Xien

Zhuang Ke

Huang Yao

Luo Xuan

Chen Yanmeng

Huang Ailong

Related Institution

Medical College of Wuhan University of Science and Technology

Department of Infectious Diseases， Puren Hospital Affiliated to Wuhan University of Science and Technology

Department of Infectious Diseases， Zhongnan Hospital of Wuhan University

Center for Animal Experiment/Animal Biosafety Level-III Laboratory， Wuhan University

Key Laboratory of Molecular Biology on Infectious Disease,Ministry of Education,Chongqing Medical University

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