Schramm Frédéric, Soulier Eric, Royer Cathy, Weitten Thierry, Fafi-Kremer Samira, Brignon Nicolas, Meyer Nicolas, Ellero Bernard, Woehl-Jaegle Marie-Lorraine, Meyer Carole, Wolf Philippe, Doffoël Michel, Baumert Thomas F, Stoll-Keller Françoise, Schvoerer Evelyne
Institut National de la Santé et de la Recherche Médicale Unité 748, Faculté de Médecine, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France.
J Infect Dis. 2008 Dec 1;198(11):1656-66. doi: 10.1086/592986.
Nonrandom distribution of hepatitis C virus (HCV) quasispecies (compartmentalization between blood plasma and leukocytes) suggests the presence of HCV leukotropic variants. HCV compartmentalization in the setting of liver transplantation (LT) is poorly understood. To study HCV leukotropic variants, we investigated the evolution of HCV compartmentalization after immunosuppression in liver transplant recipients.
Plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 5 liver transplant recipients before and after LT. We used clone sequencing to analyze the hypervariable region 1 (HVR1)-E2(384-419) region, which plays a key role in HCV entry and the induction of neutralizing responses, and assessed compartmentalization through phylogenetic analyses and Mantel's test.
Compartmentalization was frequent in the LT setting. HCV quasispecies were more homogeneous after LT in both the plasma and PBMC compartments, with a significant decrease in quasispecies complexity (P = .003) and genetic distances (P = .004) after transplantation. Our analysis identified 8 PBMC-related amino acid residues in HVR1.
HCV compartmentalization between plasma and PBMCs and the emergence of leukotropic variants could be potentiated by immunosuppression in liver transplant recipients. The identification of defined leukotropic variants may contribute to the understanding of virus-host interactions after transplantation.
丙型肝炎病毒（HCV）准种的非随机分布（血浆与白细胞之间的区室化）提示存在嗜白细胞的HCV变异体。肝移植（LT）背景下的HCV区室化情况了解甚少。为了研究嗜白细胞的HCV变异体，我们调查了肝移植受者免疫抑制后HCV区室化的演变。
从5例肝移植受者LT前后采集血浆和外周血单个核细胞（PBMC）样本。我们使用克隆测序分析高变区1（HVR1）-E2（384-419）区域，该区域在HCV进入和中和反应诱导中起关键作用，并通过系统发育分析和Mantel检验评估区室化。
在LT背景下区室化很常见。LT后血浆和PBMC区室中的HCV准种均更具同质性，移植后准种复杂性（P = .003）和遗传距离（P = .004）显著降低。我们的分析在HVR1中鉴定出8个与PBMC相关的氨基酸残基。
肝移植受者的免疫抑制可能会增强血浆和PBMC之间的HCV区室化以及嗜白细胞变异体的出现。确定的嗜白细胞变异体的鉴定可能有助于理解移植后的病毒-宿主相互作用。
