Evolution of hepatitis B genotype C viral quasi-species during hepatitis B e antigen seroconversion
Evolution of hepatitis B genotype C viral quasi-species during hepatitis B e antigen seroconversion
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DOI：
10.1016/j.jhep.2010.06.018
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发表时间：
2011-01-01
影响因子：
25.7
通讯作者：
Yokosuka, Osamu
中科院分区：
文献类型：
--
作者：
Wu, Shuang;Imazeki, Fumio;Yokosuka, Osamu
背景和目标：虽然病毒准种的演变可能与疾病的病理状态有关，但对B型肝炎中的这种现象，特别是关于B型肝炎e抗原（HBeAg）血清转换的情况知之甚少。在5个时间点分析了4组慢性B型肝炎患者、干扰素诱导的血清转换者、慢性乙型肝炎患者和慢性乙型肝炎患者中的B型肝炎病毒（HBV）X/前C/核心区的核苷酸序列。在平均60个月期间随访了IS（N = 9）、干扰素无应答者（IN，N = 9）、自发血清转换者（SS，N = 9）和无血清转换者（SN，N = 9）。结果：1800个核苷酸序列分析表明，血清转换者之间的核苷酸遗传距离无统计学差异（IS和SS;分别为6.9 x 10（-3）替换（st）/位点和6.7 x 10（-3）st/位点）和非血清转换者的那些（IN和SN;分别为5.3 x 10（-3）st/部位和3.8 x 10（-3）st/部位）。与非血清转换者相比（IN和SN;分别为5.1 × 10（-3）st/位点和5.9 × 10（-3）st/位点），血清转换者的序列多样性（IS和SS;分别为10.9 × 10（-3）st/位点和9.9 × 10（-3）st/位点）在血清转换后显著升高（p < 0.05），并且在血清转换后的血清转换者中高于血清转换前（p < 0.05），而在观察期间，在非血清转换者中这变化很小。系统发育树显示出更大的复杂性secoconversion比非血清转换。在HBeAg血清转换前，对后代和祖先之间序列变化方向的简约性估计显示，血清转换者中有更高频率的A-T交叉置换（0.06对0.02，p = 0.0036），这与具有A1762 T突变的准种的动态一致。血清转换后HBeAg血清转换者中明显更大的病毒多样性可能与更强的选择压力导致的逃逸突变体有关。(C)2010年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Although the evolution of viral quasi-species may be related to the pathological status of disease, little is known about this phenomenon in hepatitis B, particularly with respect to hepatitis B e antigen (HBeAg) seroconversion.Methods: Nucleotide sequences of the hepatitis B virus (HBV) X/precore/core region was analyzed at five time-points in four groups of chronic hepatitis B patients, interferon-induced seroconverters (IS, N = 9), interferon non-responders (IN, N = 9), spontaneous seroconverters (SS, N = 9), and non-seroconverters (SN, N = 9) followed during 60 months on an average. Only patients with genotype C were studied.Results: Analysis of 1800 nucleotide sequences showed that there was no statistical difference between the nucleotide genetic distances of seroconverters (IS and SS; 6.9 x 10(-3) substitutions (st)/site and 6.7 x 10(-3) st/site, respectively) and those of non-seroconverters (IN and SN; 5.3 x 10(-3) st/site and 3.8 x 10(-3) st/site, respectively) before seroconversion. Compared to non-seroconverters (IN and SN; 5.1 x 10(-3) st/site and 5.9 x 10(-3) st/site, respectively), the sequence diversity of seroconverters (IS and SS; 10.9 x 10(-3) st/site and 9.9 x 10(-3) st/site, respectively) was significantly higher after seroconversion (p < 0.05), and was higher in seroconverters after seroconversion than before seroconversion (p < 0.05), while this changed very little in non-seroconverters during the observation period. Phylogenetic trees showed greater complexity in secoconverters than non-seroconverters. Parsimony-based estimation of the direction of sequence change between descendants and ancestors before HBeAg seroconversion, revealed higher frequencies of transversional A to T substitution in seroconverters (0.06 vs. 0.02, p = 0.0036) that coincided with the dynamics of quasi-species possessing A1762T mutation.Conclusions: The distinctly greater viral diversity in HBeAg seroconverters after seroconversion could be related to escape mutants resulting from stronger selection pressure. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.