Dynamics of Defective Hepatitis C Virus Clones in Reinfected Liver Grafts in Liver Transplant Recipients: Ultradeep Sequencing Analysis
Dynamics of Defective Hepatitis C Virus Clones in Reinfected Liver Grafts in Liver Transplant Recipients: Ultradeep Sequencing Analysis
复制标题
DOI：
10.1128/jcm.00676-13
复制
发表时间：
2013-11-01
影响因子：
9.4
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
--
作者：
Ohtsuru, Shigeru;Ueda, Yoshihide;Chiba, Tsutomu
丙型肝炎病毒 (HCV) 在移植后立即复制，重新感染移植受者的同种异体肝移植物，导致血清 HCV RNA 水平迅速升高。我们评估了移植肝再次感染 HCV 后病毒遗传复杂性的动态变化；我们还利用大规模并行超深测序技术确定了复制HCV克隆的特征，以确定肝移植前后5名基因型1b HCV感染的移植受者的肝脏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，并且个体的肝脏和血清标本中的HCV群体构成没有显着差异。肝移植后血清中的病毒准种复杂度明显低于肝移植前，表明某些HCV克隆在移植后选择性增殖。缺乏HCV基因组结构区域的缺陷HCV克隆的数量没有增加，而全基因组HCV克隆在肝移植后立即选择性地增加数量。一名患者在移植后 22 个月检测到移植前存在的相同缺陷克隆再次增加。超深测序技术揭示肝移植后HCV遗传异质性降低。肝移植后缺陷型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。
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.