Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation.
Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation.
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DOI：
10.1084/jem.20090766
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发表时间：
2010-08-30
期刊：
影响因子：
--
通讯作者：
Baumert TF
中科院分区：
文献类型：
--
作者：
Fafi-Kremer S;Fofana I;Soulier E;Carolla P;Meuleman P;Leroux-Roels G;Patel AH;Cosset FL;Pessaux P;Doffoël M;Wolf P;Stoll-Keller F;Baumert TF
慢性丙型肝炎病毒感染引起的终末期肝病是肝移植的主要原因。由于病毒逃避宿主免疫反应和缺乏预防性抗病毒策略，移植物的再次感染是普遍存在的。病毒逃避宿主免疫以再次感染肝移植的机制尚不清楚。在对六名接受肝移植的丙型肝炎病毒感染患者的纵向分析中，我们证明，与移植后未检测到的变异株相比，移植前血清中存在的抗体对再次感染肝移植的丙型肝炎病毒变异株具有有效的进入和较差的中和作用。针对丙型肝炎病毒包膜糖蛋白或细胞进入因子的单抗有效地交叉中和患者来源的对自体宿主中和反应具有抵抗力的病毒株对人类肝细胞的感染。这些发现对丙型肝炎病毒再感染过程中病毒逃逸的分子机制提供了重要的见解，并表明病毒进入是预防肝移植丙型肝炎病毒再感染的一个可行的靶点。
End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.
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