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  

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

作　　者：邓海君[1] 黄勇[2] 龙泉鑫[1] 黄爱龙[1] 

机构地区：[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,重庆400016 [2]重庆医科大学附属第二医院检验科,重庆400012

出　　处：《重庆医科大学学报》2016年第1期76-80,共5页Journal of Chongqing Medical University

基　　金：传染病十二五重大专项资助项目(编号:2013ZX10002002);国家自然科学基金资助项目(编号:81301394);重庆市科委自然科学基金资助项目(编号:cstc2013jcyj C10002和csts2013jcyja10064)

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。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 

分 类 号：R373.2[医药卫生—病原生物学]