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隱匿性乙型肝炎病毒感染患者S基因突變特點分析

發(fā)布時間:2018-05-27 08:01

  本文選題:肝炎病毒 + 乙型 ; 參考:《解放軍醫(yī)學(xué)雜志》2015年03期


【摘要】:目的分析1例血清HBV DNA長期陽性但HBsAg陰性的隱匿性乙型肝類病毒感染(OBI)患者HBV S基因突變特點,揭示S基因突變與OBI發(fā)生及肝臟疾病進(jìn)展的關(guān)系。方法收集該患者不同時間點的4份血清樣本,擴(kuò)增HBV S基因并進(jìn)行克隆測序,挑選代表性突變株病毒基因構(gòu)建重組載體并進(jìn)行表型分析。結(jié)果從該患者4份血清樣本中檢出多種S基因突變形式,包括前S1區(qū)大片段缺失、s126 127"RPCMNCTI"插入突變、sQ129N、s131 133 TSM→NST和經(jīng)典的sG145R突變等,其中s131 133 TSM→NST在前后4份動態(tài)樣本的檢測病毒克隆中所占比例分別為0%、26%、59%和74%;前S1區(qū)大片段缺失在4份樣本檢測病毒克隆中始終存在,所占比例分別為26%、17%、15%和21%。表型分析發(fā)現(xiàn),sQ129N和s131 133 TSM→NST可以降低抗體對HBsAg的親和力,增加病毒分泌;與野生株相比,前S1區(qū)大片段(nt 3046 3177)缺失病毒株復(fù)制力下降了43.7%,表面抗原啟動子Ⅱ(SPⅡ)活性下降了97.2%;sG145R可降低病毒的分泌能力。結(jié)論此例HBV感染患者的長期OBI臨床表現(xiàn)是由于其感染有多種S基因突變病毒株引起,其中一些S基因突變可以影響病毒的表型特點,可能與肝臟疾病進(jìn)展密切相關(guān)。
[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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