隐匿性乙型肝炎病毒感染患者S基因突变特点分析

发布时间：2018-05-27 08:01

  本文选题：肝炎病毒 + 乙型　； 参考：《解放军医学杂志》2015年03期

【摘要】：目的分析1例血清HBV DNA长期阳性但HBsAg阴性的隐匿性乙型肝类病毒感染(OBI)患者HBV S基因突变特点,揭示S基因突变与OBI发生及肝脏疾病进展的关系。方法收集该患者不同时间点的4份血清样本,扩增HBV S基因并进行克隆测序,挑选代表性突变株病毒基因构建重组载体并进行表型分析。结果从该患者4份血清样本中检出多种S基因突变形式,包括前S1区大片段缺失、s126 127"RPCMNCTI"插入突变、sQ129N、s131 133 TSM→NST和经典的sG145R突变等,其中s131 133 TSM→NST在前后4份动态样本的检测病毒克隆中所占比例分别为0%、26%、59%和74%;前S1区大片段缺失在4份样本检测病毒克隆中始终存在,所占比例分别为26%、17%、15%和21%。表型分析发现,sQ129N和s131 133 TSM→NST可以降低抗体对HBsAg的亲和力,增加病毒分泌;与野生株相比,前S1区大片段(nt 3046 3177)缺失病毒株复制力下降了43.7%,表面抗原启动子Ⅱ(SPⅡ)活性下降了97.2%;sG145R可降低病毒的分泌能力。结论此例HBV感染患者的长期OBI临床表现是由于其感染有多种S基因突变病毒株引起,其中一些S基因突变可以影响病毒的表型特点,可能与肝脏疾病进展密切相关。
[Abstract]:Objective to analyze the characteristics of HBV S gene mutation in a patient with long term positive serum HBV DNA but negative HBsAg in order to reveal the relationship between the mutation of S gene and the occurrence of OBI and the progression of liver disease. Methods four serum samples were collected from the patients at different time points, HBV S gene was amplified, cloned and sequenced. The recombinant vector was constructed and phenotypic analysis was carried out. Results A variety of S gene mutations were detected from 4 serum samples of the patient, including the large deletion of preS1 region, s126 "127" RPCMNCTI "insertion mutation, sQ129Nnm131 / 133 TSM NST and classical sG145R mutation, etc. Among them, the proportion of s131n133 TSM NST in virus clones of 4 dynamic samples was 0, 2659% and 74%, respectively, and the deletion of large fragment in preS1 region was always present in 4 samples, accounting for 26171715% and 21.1%, respectively. Phenotypic analysis showed that SQ129N and s131O133 TSM NST could reduce the affinity of antibody to HBsAg and increase the secretion of virus, and compared with the wild strains, The replication ability of the deleted virus strain was decreased by 43.7%, and the activity of surface antigen promoter 鈪，

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