Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection
Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection
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DOI：
10.1053/jhep.2001.21163
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发表时间：
2001-01-01
期刊：
影响因子：
13.5
通讯作者：
Su, IJ
中科院分区：
文献类型：
--
作者：
Fan, YF;Lu, CC;Su, IJ
在慢性B型肝炎病毒（HBV）感染患者的血清或肝组织中，已鉴定出几种类型的天然前S突变体。为了阐明前S突变体出现的普遍性和意义，研究了140例HBV患者血清和18例切除的肝脏。根据血清中HBV-DNA水平或肝脏中HBV抗原的表达将复制状态指定为高、中、低。进行体外转染和Western印迹分析以表征突变体构建体的HBsAg表达和分泌。在血清和肝脏中鉴定出五种主要类型（I至V）的前S缺失突变体，在肝脏中鉴定出两种类型（VI和VII）。血清中Pre-S突变体在高复制期占6.4%，在中间复制期占13%，在低复制期或非复制期占37.5%。在肝脏中，存在相同的趋势：前S2缺失突变体出现并在低复制阶段在肝细胞中流行，表达一种新的HBsAg边缘模式，通常聚集在组中。前S2区的缺失序列与人白细胞抗原限制性T细胞和B细胞表位一致，大部分前S区突变体的HBsAg保留在肝细胞内，主要表面抗原的合成和分泌减少。Pre-S突变体在慢性HBV的演变中占主导地位，可能是在免疫压力下。前S突变体的出现可能是HBV血清和肝脏中HBsAg终身持续存在和差异的原因，并且鉴于携带前S2突变体的肝细胞的聚集性增殖可能赋予生长优势。
Several types of naturally occurring pre-S mutants in sera or liver tissues in patients with chronic hepatitis B virus (HBV) infection have been identified. To clarify the prevalence and significance of emergence of pre-S mutants, 140 sera and 18 resected livers from patients with HBV were studied. Replicative status was designated as high, intermediate, and low based on the HBV-DNA levels in serum or the expression of HBV antigens in liver, In vitro transfection and Western blot analysis were performed to characterize expression and secretion of HBsAg by the mutant constructs. Five major types (I to V) of pre-S deletion mutants in serum and liver and 2 types (VI and VII) in liver were identified. Pre-S mutant was 6.4% at high replicative phase, 13% at intermediate, and 37.5% at low or nonreplicative phases in serum. In livers, the same tendency existed: pre-S2 deletion mutants emerged and prevailed at a low replicative phase in hepatocytes that expressed a novel marginal pattern of HBsAg and usually clustered in groups. The deletion sequence of pre-S2 region coincides with human leukocyte antigen-restricted T- and B-cell epitopes, In vitro HBsAg was retained in the hepatocytes and synthesis and secretion of major surface antigen decreased for most of the pre-S mutants. Pre-S mutants prevailed with evolution of chronic HBV, probably under immune pressure. Emergence of pre-S mutants may account for the life-long persistence and discrepancy of HBsAg in serum and liver in HBV and may confer growth advantage in view of the clustering proliferation of hepatocytes harboring pre-S2 mutant.