慢性乙型肝炎感染者HBV Pre-S/S基因变异特征分析  被引量:1

Pre-S/S gene variants of hepatitis B virus in patients with chronic HBV infection

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作  者:李东[1] 潘伟毅[1,2] 张苏晗 杨秀惠 陈致飞[1] 郑凝旋[1] 周勇 

机构地区:[1]福建省疾病预防控制中心福建省人兽共患病重点实验室,福建福州350001 [2]福建医科大学公共卫生学院教学基地,福建福州350001

出  处:《中国热带医学》2017年第12期1167-1172,共6页China Tropical Medicine

基  金:国家科技重大专项课题(No.2012ZX10002001-002-002);泉州市科技计划项目(No.2015Z43)

摘  要:目的探讨慢性乙型肝炎感染者HBV Pre-S/S基因序列特征及不同抗原表位氨基酸的变异情况。方法采用巢式PCR法分片段扩增HBV-DNA阳性的慢性乙型肝炎感染者HBV的Pre-S/S基因,并对扩增产物进行测序,将测序结果与Gen Bank中的标准序列比对分析。结果 120例HBV感染者中B基因型78例,C基因型42例。序列分析发现,B基因型中有2例出现Pre-S1基因序列缺失;C基因型中有1例出现Pre-S2基因序列缺失。Pre-S/S蛋白区抗原表位变异分析可知,除CTL的3个抗原表位(CTL-7、8、9)外,其它检测的抗原表位均出现变异。相关性分析发现,除B细胞4、5表位,CTL 4、5表位及Th细胞1表位的变异与样品的基因型具有一定的相关性(P<0.05),其它表位的变异与样品基因型无统计学意义。抗原表位具体氨基酸变异分析发现,Pre-S1/S2基因位点如27、45、46、48等氨基酸变异可导致多个抗原表位同时发生变异;在"a"决定簇中还发现126、129、131、133、144、145等热门位点的变异,B基因型中有2例发生G145R经典逃逸株的变异;C基因型中发现7例与严重肝病有一定相关性的I126T位点变异。结论慢性乙型肝炎感染者HBV Pre-S/S基因上也普遍存在基因变异,其中包括G145R、I126T等热门突变位点,这些位点的氨基酸突变可导致Pre-S/S蛋白区一个或多个抗原表位的改变,进而影响其免疫原性,并导致HBV逃避宿主的免疫监视而引起持续感染。Objective To explore the sequence characteristics of HBV Pre-S/S gene and the variation of amino acid indifferent epitopes of chronic hepatitis B infection persons. Methods The Pre-S/S gene from HBV DNA positive patientswere amplified and sequenced directly by nested PCR, and then these sequence results were compared with the consensussequences in Gen Bank. Results In all 120 patients, 78 were B genotype and 42 were C genotype. The sequence analysisshowed that two of the B genotypes had a deletion of the Pre-S1 gene sequence. One of the C genotypes had a deletion of the Pre-S2 gene sequence. Pre-S/S protein epitope variation analysis showed that all of antigen epitopes were mutated, except theCTL three antigen epitopes(CTL-7, 8, 9). The correlation analysis showed that the mutations of the 4 and 5 epitopes in B celland CTL and Th cells 1 epitopes were correlated with the genotype of the samples(P〈0.05). The amino acid variation of theepitope of the Pre-S1/S2 gene, such as 27, 45, 46, 48, could lead to the variation of multiple epitopes. In addition, themutations of 126, 129, 131, 134, 145 and other popular loci were also found in the "a" determinant, among which 2 mutationsof G145 R were found in B gene samples; 7 cases were found mutations of I126 T in the C genotype sample with a certaindegree of correlation with severe liver disease. Conclusion G145 R, I126 T and other popular mutation sites also exist in theearly chronic hepatitis B infection Pre-S/S gene, these sites of amino acid mutation can lead to Pre-S/S protein epitopechanges, and thus affect its immunogenicity leading to HBV immune surveillance to escape the host and cause persistentinfection.

关 键 词:乙型肝炎病毒 Pre-S/S基因 抗原表位 变异 

分 类 号:R512.6[医药卫生—内科学]

 

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