Longitudinal evaluation of the structure of replicating and circulating hepatitis C virus quasispecies in nonprogressive chronic hepatitis C patients
Longitudinal evaluation of the structure of replicating and circulating hepatitis C virus quasispecies in nonprogressive chronic hepatitis C patients
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DOI：
10.1128/jvi.75.24.12005-12013.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Gómez, J
中科院分区：
文献类型：
--
作者：
Cabot, B;Martell, M;Gómez, J
在以前的横断面研究中，我们证明，在大多数慢性丙型肝炎患者中，循环丙型肝炎病毒（HCV）群体的组成和复杂性与肝脏中复制的病毒不一致。在两个室中具有相似复杂性的患者亚组中，配对样本的肝脏与血清中的准种复杂性比率（肝脏/血清复杂性比率）与疾病阶段相关。在本研究中，我们调查了连续配对的肝脏和血清样本中病毒群体参数的动态行为，这些样本来自4名转氨酶持续正常且肝组织学稳定的慢性丙型肝炎患者，间隔3至6年。我们对包含E2（p7）-NS 2连接的基因组片段的359个克隆进行了测序，这些克隆来自4名患者的两个连续的肝脏血清样本对和来自其中一名患者的4个中间血清样本。结果表明，肝脏/血清复杂性比率并不稳定，而是随时间大幅波动。因此，肝脏/血清复杂性比率不能识别特定的患者组，而是识别感染准种的特定状态。系统发育分析和特征突变模式表明，几乎所有的循环序列起源于肝脏标本中存在的序列。循环病毒准种的总体行为似乎起源于感染肝脏中存在的大突变谱的相对复制动力学的变化。
In previous cross-sectional studies, we demonstrated that, in most patients with chronic hepatitis C, the composition and complexity of the circulating hepatitis C virus (HCV) population do not coincide with those of the virus replicating in the liver. In the subgroup of patients with similar complexities in both compartments, the ratio of quasispecies complexity in the liver to that in serum (liver/serum complexity ratio) of paired samples correlated with disease stage. In the present study we investigated the dynamic behavior of viral population parameters in consecutive paired liver and serum samples, obtained 3 to 6 years apart, from four chronic hepatitis C patients with persistently normal transaminases and stable liver histology. We sequenced 359 clones of a genomic fragment encompassing the E2(p7)-NS2 junction, in two consecutive liver-serum sample pairs from the four patients and in four intermediate serum samples from one of the patients. The results show that the liver/serum complexity ratio is not stable but rather fluctuates widely over time. Hence, the liver/serum complexity ratio does not identify a particular group of patients but a particular state of the infecting quasispecies. Phylogenetic analysis and signature mutation patterns showed that virtually all circulating sequences originated from sequences present in the liver specimens. The overall behavior of the circulating viral quasispecies appears to originate from changes in the relative replication kinetics of the large mutant spectrum present in the infected liver.