Hughes Michael G, Chong Tae W, Smith Robert L, Evans Heather L, Iezzoni Julia C, Sawyer Robert G, Rudy Christine K, Pruett Timothy L
Department of Surgery, Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville, Virginia, USA.
Am J Transplant. 2005 Oct;5(10):2504-13. doi: 10.1111/j.1600-6143.2005.01060.x.
The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients. Clones of RT-PCR product were directly sequenced to identify HVR1 quasispecies variants. Explanted liver and serial allograft biopsies in recipients with HCV were examined by immunohistochemistry (IHC) for CD81 expression. Examination of HVR1 sequences demonstrated that only a fraction of the quasispecies variants recovered from each patient's blood sampled immediately prior to transplantation associated with and infected the allografts. Genetic diversity at HVR1 decreased with reperfusion but did not significantly decrease with infection. Expression of CD81 varied during the immediate post-transplant period. In conclusion, HVR1 quasispecies variants differentially associate with, and infect allografts, after liver transplantation. Additionally, allografts express variable amounts of CD81 after transplantation.
位于高变区1（HVR1）的第二种包膜蛋白被认为参与丙型肝炎病毒（HCV）与宿主细胞的相互作用，并且已证实CD81（一种多功能蛋白）作为HCV的细胞表面受体，可能直接与HVR1相互作用。本研究的目的是确定某些HVR1准种变体在肝移植后是否比其他HVR1变体更有效地与同种异体移植物结合并感染，以及移植后CD81受体表达是否发生变化。从7例患者移植期间采集血液和同种异体移植物样本。对RT-PCR产物的克隆进行直接测序以鉴定HVR1准种变体。对丙型肝炎病毒感染受者的离体肝脏和系列同种异体移植活检组织进行免疫组织化学（IHC）检测CD81表达。对HVR1序列的检测表明，从每位患者移植前即刻采集的血液中回收的准种变体中，只有一部分与同种异体移植物结合并感染。HVR1的基因多样性随再灌注而降低，但不随感染而显著降低。移植后即刻CD81的表达有所变化。总之，肝移植后HVR1准种变体与同种异体移植物的结合及感染存在差异。此外，同种异体移植物移植后表达不同量的CD81。
