SR-BI及其伴侣分子PDZK1在HCV入侵中的作用

The function of SR-BI and chaperone PDZK1 in the entry of HCV

B族Ⅰ型清道夫受体(scavenger receptor class B type I,SR-BI)是丙型肝炎病毒(hepatitis C virus,HCV)的受体之一,可以与HCV的包膜蛋白E2结合,介导病毒颗粒进入宿主细胞。伴侣分子PDZK1(PDZdomain containing 1)是一个含有4个PDZ结构域的支架蛋白,其第一个PDZ结构域可以与SR-BI的C端结合,调节其稳定表达和正确定位。研究发现PDZK1基因敲除以后,HCVcc(cell culture produced HCVvirus)和HCVpp(HCV pseudotype particles)的感染性明显下降;重新转入PDZK1后,可以部分恢复感染性。研究表明PDZK1可促进HCV入侵并可能是通过与SR-BI的相互作用介导的。伴侣分子对受体分子的调节在HCV入侵中的作用可能成为HCV治疗的潜在靶标,有助于开发新的治疗方法。

SR-BI（scavenger receptor class B type I） is a receptor binding to the envelope protein E2 of HCV to mediate the particle entry into host cell.PDZK1 is a scaffold protein containing four PDZ protein interaction domains.Binding to the carboxy termini of SR-BI through its PDZ1 domain,PDZK1 can modulate the stable expression and accurate localization of SR-BI.Recently,there is a striking finding that the infectivity of HCVcc（cell culture produced HCV virus） and HCVpp（HCV pseudotype particles） decreased after knocking out of PDZK1,while retransferring PDZK1 could partially restore infectivity.The data showed that PDZK1 could promote HCV entry and might be functioned by interaction with SR-BI.The chaperone’s modulating effect on the HCV receptor can be used as a potential treatment target,and is helpful to develop a new effective treatment for HCV infection.