Anti-CD81 Antibodies Can Prevent a Hepatitis C Virus Infection In Vivo
Anti-CD81 Antibodies Can Prevent a Hepatitis C Virus Infection In Vivo
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DOI：
10.1002/hep.22547
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发表时间：
2008-12-01
期刊：
影响因子：
13.5
通讯作者：
Leroux-Roels, Geert
中科院分区：
文献类型：
--
作者：
Meuleman, Philip;Hesselgesser, Joseph;Leroux-Roels, Geert
丙型肝炎病毒(丙型肝炎病毒)的病毒生命周期主要通过不同的体外细胞培养模型进行研究。使用伪病毒颗粒(HCVpp)和最近的细胞培养衍生病毒(HCVcc)的研究表明，至少有三个宿主细胞分子对丙型肝炎病毒的体外进入至关重要：Tetraspanin CD81，清道夫受体B类成员I和紧密连接蛋白Claudin-1。这些受体对体内感染是否同样重要仍有待证实。我们表明，CD81对于真实的体内丙型肝炎病毒感染是必不可少的。抗CD81抗体的预防性治疗完全保护了人类肝-uPA-SCID小鼠免受不同基因型丙型肝炎病毒共同毒株的后续攻击。病毒攻击后给予抗CD81抗体无效。结论：我们的实验为CD81在体内真正的丙型肝炎病毒感染中的关键作用提供了证据，并为预防慢性感染的丙型肝炎患者原位肝移植后再感染开辟了新的视角。(《肝病》2008；48：1761-1768。)
The viral life cycle of the hepatitis C virus (HCV) has been studied mainly using different in vitro cell culture models. Studies using pseudoviral particles (HCVpp) and more recently cell culture-derived virus (HCVcc) suggest that at least three host cell molecules are important for HCV entry in vitro: the tetraspanin CD81, the scavenger receptor class B member I, and the tight junction protein Claudin-1. Whether these receptors are equally important for an in vivo infection remains to be demonstrated. We show that CD81 is indispensable for an authentic in vivo HCV infection. Prophylactic treatment with anti-CD81 antibodies completely protected human liver-uPA-SCID mice from a subsequent challenge with HCV consensus strains of different genotypes. Administration of anti-CD81 antibodies after viral challenge had no effect. Conclusion: Our experiments provide evidence for the critical role of CD81 in a genuine HCV infection in vivo and open new perspectives for the prevention allograft reinfection after orthotopic liver transplantation in chronically infected HCV patients. (HEPATOLOGY 2008;48:1761-1768.)