Analysis of hepatitis C viral quasispecies in liver transplantation
Analysis of hepatitis C viral quasispecies in liver transplantation
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DOI：
10.1016/s0041-1345(03)00632-8
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发表时间：
2003-08-01
影响因子：
0.9
通讯作者：
Marugan, RB
中科院分区：
文献类型：
--
作者：
Garcia, JM;Terron, SD;Marugan, RB
丙型肝炎病毒 (HCV) 是一种以高突变率复制的 RNA 病毒，尤其是在高变区 1 (HVR-1) 中。连续的病毒突变导致混合且不断变化的突变体群体，称为准种。 HCV 准种的性质可能对病毒持久性和病原体有影响。对肝移植患者的研究表明，免疫抑制程度与准种的复杂性之间存在关系。本研究评估了与免疫功能正常的 HCV 患者相比，免疫抑制治疗是否会改变肝移植受者中 HCV 准种的进化。研究分为两组：11 名因 HCV 相关肝硬化接受 OLT 的患者和 10 名对照组患者。获取每位患者的两份血清样本，通过 RT-PCR 分析 HCV HVR1 区域。 SSCP 分析未能显示基础时间点和最终时间点或移植前与移植后的准种数量存在统计学显着差异（对照患者分别为 7.3 +/- 2 与 6.7 +/- 3，移植患者分别为 4.4 +/- 2 与 4.1 +/- 1）。对照组（分别为 2.8 +/- 2 与 2.3 +/- 2）或移植组（分别为 2.5 +/- 2 与 2.2 +/- 1）中缺失或新变异之间没有观察到显着差异。根据序列分析，移植患者 OLT 后样本的遗传复杂性显着降低（0.057 +/- 0.04 [移植前] vs 0.035 +/- 0.02 [移植后]；P = 0.048）。然而，对照患者的基础样本与最终样本没有发现显着差异（分别为 0.04 +/- 0.03 与 0.066 +/- 0.04）。我们的研究结果似乎表明，接受肝移植的患者的病毒准种多样性较低。
The hepatitis C virus (HCV) is an RNA virus that replicates with a high rate of mutation, especially in the hypervariable region 1 (HVR-1). Continuous viral mutations lead to a mixed and changing populations of mutants, called quasispecies. The nature of the HCV quasispecies may have implications for viral persistence and pathogenies. Studies with liver transplant patients suggest a relationship between the degree of immunosuppression and the complexity of the quasispecies. This study evaluated whether immunosuppressive therapy modifies the evolution of HCV quasispecies among liver transplant recipients compared with immunocompetent HCV patients. Two groups were studied: 11 patients who underwent OLT for HCV-related cirrhosis and 10 control group patients. Two serum samples from each patient were obtained to analyze the HCV HVR1 region by RT-PCR. SSCP analysis failed to show statistically significant differences in the number of quasispecies at basal and final time points or at pretransplant versus posttransplant (7.3 +/- 2 vs 6.7 +/- 3 in control patients, respectively, and 4.4 +/- 2 vs 4.1 +/- 1 in transplanted patients, respectively). No significant difference was observed between missing or new variants in the control (2.8 +/- 2 vs 2.3 +/- 2, respectively) or transplanted group (2.5 +/- 2 vs 2.2 +/- 1, respectively). Upon sequence analysis, the genetic complexity was significantly lower among samples after OLT in transplanted patients (0.057 +/- 0.04 [pretransplant] vs 0.035 +/- 0.02 [posttransplant]; P = .048). However, no significant differences were found among control patients in basal versus final samples (0.04 +/- 0.03 vs 0.066 +/- 0.04, respectively). Our findings seem to demonstrate that viral quasispecies diversity is lower among patients receiving a liver transplant.