Nucleotide and amino acid complexity of hepatitis C virus quasispecies in serum and liver
Nucleotide and amino acid complexity of hepatitis C virus quasispecies in serum and liver
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DOI：
10.1128/jvi.74.2.805-811.2000
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发表时间：
2000-01-01
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
丙型肝炎病毒（HCV）的准种性质被认为在维持和调节病毒复制中发挥核心作用。几项研究试图通过表征HCV循环准种的参数来阐明该疾病的预后标志物。在以前的工作中，我们证明了循环病毒准种的参数并不总是反映肝内病毒。在这里，我们分析了配对的血清和肝脏准种从39个基因型1b感染患者不同程度的肝损伤，从最小的变化到肝硬化。通过实时逆转录-PCR定量病毒水平，并通过对包含E2-NS 2连接的基因组片段的540种HCV变体进行克隆和测序来表征病毒异质性。虽然在95%的患者中，血清和肝脏的共识HCV氨基酸序列是相同的，准种的复杂性之间的差异很大，从每个隔室分离的病毒。血清中HCV准种的复杂性（26%）高于、低于或相似（41%）肝组织中HCV准种，其中肝纤维化与所有测量病毒氨基酸复杂性的参数显著相关，肝纤维化与血清病毒载量也相关（R = 0.7）。关于血清和肝脏群体之间准种复杂性差异的起源，序列分析反对肝外复制作为定量的重要贡献因素，并支持对病毒的差异效应或不同选择力的想法，这取决于它是否在血清中循环或在肝脏中复制。
The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated from each compartment. Patients with HCV quasispecies in serum more complex (26%) than, less complex (28%) than, or similarly complex (41%) to those in liver were found. Among the last, a significant correlation between fibrosis and all the parameters that measure the viral amino acid complexity was found. Correlation between fibrosis and serum viral load was found as well (R = 0.7). With regard to the origin of the differences in quasispecies complexity between serum and liver populations, sequence analysis argued against extrahepatic replication as a quantitatively important contributing factor and supported the idea of a differential effect or different selective forces on the virus depending on whether it is circulating in serum or replicating in the liver.