Naturally occurring hepatitis B surface gene variants in chronic hepatitis B virus infection: Correlation with viral serotypes and clinical stages of liver disease
Naturally occurring hepatitis B surface gene variants in chronic hepatitis B virus infection: Correlation with viral serotypes and clinical stages of liver disease
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DOI：
10.1002/jmv.10169
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发表时间：
2002-09-01
影响因子：
12.7
通讯作者：
Chen, DS
中科院分区：
文献类型：
--
作者：
Liu, CJ;Kao, JH;Chen, DS
病毒变异株逃避宿主免疫可能与乙肝病毒感染的发病机制有关。在这项横断面研究中，评估了表面基因免疫原性表位内氨基酸变异的频率与慢性乙肝病毒感染的不同疾病阶段之间的关系。对33例无症状携带者(组1)、31例慢性肝炎(组11)、22例肝硬变(组111)和36例肝细胞癌(组IV)患者的HBVa表位基因(氨基酸124-148)和人类白细胞抗原I类限制性细胞毒性T淋巴细胞(CTL)表位(氨基酸28-51)进行了扩增和直接测序。氨基酸序列与乙肝病毒血清型ADW或ADR的共同序列进行比较。根据临床和病毒学特征分层后，用Poisson模型广义估计方程分析每序列每位点氨基酸变异频率(FEQ)。FEQ总体为1.21%，在IV组患者和50岁以上患者中最高。而5 0岁以下感染ADW型的IV组患者的FEQ显著高于5 0岁以上的患者，肝癌患者的FEQ与非肿瘤患者的FEQ差异有统计学意义(P=0.0 4)。ADW血清型的决定簇和CTL表位内的氨基酸变异，而ADR血清型的氨基酸是随机分布的。ADW血清型和ADR血清型突变热点不同。乙肝病毒表面蛋白FEQ与年龄和肝病严重程度呈正相关，某些变异可能与乙肝病毒感染的持续性有关。(C)2002年Wiley-Liss，Inc.
Virus variants escaping from host immunity may be implicated in the pathogenesis of hepatitis B virus (HBV) infection. In this cross-sectional study, the association was evaluated of the frequency of amino acid variation within the immunogenic epitopes of surface gene with different disease stages of chronic HBV infection. The surface gene of HBV encompassing the a determinant (amino acids 124-148) and the putative HLA class I restricted cytotoxic T lymphocyte (CTL) epitope (amino acids 28-51) were amplified and directly sequenced in 33 asymptomatic carriers (Group 1), 31 patients with chronic hepatitis (Group 11), 22 with cirrhosis (Group 111), and 36 with hepatocellular carcinoma (Group IV). The amino acid sequences were compared subsequently with the consensus sequences of HBV serotype adw or adr. The frequency of amino acid variation per site per sequence (FEQ) was analyzed by generalized estimating equation with Poisson model after stratification by clinical and virological features. The FEQ was 1.21% overall, and was highest in Group IV patients and in patients above 50 years of age. In contrast, nine Group IV patients aged below 50 years who were infected with serotype adw had an inversely higher FEQ than those above 50; the age effect among hepatocellular carcinoma patients was significantly different from that among non-cancerous patients (P=0.04). Variation of amino acid clustered within a determinant and CTL epitope for serotype adw but was distributed at random for serotype adr. Mutation hotspots differed between serotypes adw and adr. The FEQ of HBV surface protein is correlated positively with advancing age and severity of liver disease, and certain variants may contribute to the persistence of HBV infection. (C) 2002 Wiley-Liss, Inc.