Department of Gastroenterology and Hepatology.
J Clin Microbiol. 2013 Nov;51(11):3645-52. doi: 10.1128/JCM.00676-13. Epub 2013 Aug 28.
Hepatitis C virus (HCV) reinfects liver allografts in transplant recipients by replicating immediately after transplantation, causing a rapid increase in blood serum HCV RNA levels. We evaluated dynamic changes in the viral genetic complexity after HCV reinfection of the graft liver; we also identified the characteristics of replicating HCV clones using a massively parallel ultradeep sequencing technique to determine the full-genome HCV sequences in the liver and serum specimens of five transplant recipients with genotype 1b HCV infection before and after liver transplantation. The recipients showed extremely high genetic heterogeneity before transplantation, and the HCV population makeup was not significantly different between the liver and blood serum specimens of the individuals. Viral quasispecies complexity in serum was significantly lower after liver transplantation than before it, suggesting that certain HCV clones selectively proliferated after transplantation. Defective HCV clones lacking the structural region of the HCV genome did not increase in number, and full-genome HCV clones selectively increased in number immediately after liver transplantation. A re-increase in the same defective clone existing before transplantation was detected 22 months after transplantation in one patient. Ultradeep sequencing technology revealed that the genetic heterogeneity of HCV was reduced after liver transplantation. Dynamic changes in defective HCV clones after liver transplantation indicate that these clones have important roles in the HCV life cycle.
丙型肝炎病毒 (HCV) 在移植受者中通过移植后立即复制再感染肝移植物，导致血清 HCV RNA 水平迅速升高。我们评估了 HCV 再感染肝移植物后病毒遗传复杂性的动态变化；我们还使用大规模平行超深度测序技术鉴定了复制 HCV 克隆的特征，以确定五例基因型 1b HCV 感染的移植受者肝和血清标本中的全基因组 HCV 序列。受者在移植前表现出极高的遗传异质性，个体的肝和血清标本中 HCV 群体构成无显著差异。移植后血清中的病毒准种复杂性明显低于移植前，提示某些 HCV 克隆在移植后选择性增殖。缺乏 HCV 基因组结构区的缺陷型 HCV 克隆数量没有增加，全基因组 HCV 克隆在移植后立即选择性增加。一名患者在移植后 22 个月检测到移植前存在的同一缺陷型克隆再次增加。超深度测序技术显示移植后 HCV 的遗传异质性降低。移植后缺陷型 HCV 克隆的动态变化表明这些克隆在 HCV 生命周期中具有重要作用。
