New Insights in Recurrent HCV Infection after Liver Transplantation

Hsu, Shih-Hsien; Yeh, Ming-Lun; Wang, Shen-Nien

CD81 is one of these potential targets. Imidazole-based compounds mimicking an alpha helix in the LEL of CD81 compete for HCV E2-CD81 binding [111] . These drugs bind E2 in a reversible manner and block E2-CD81 interaction while having no effect neither on CD81 expression nor on CD81 interaction with physiological partner molecules. In addition, recent study demonstrated that anti-CD81 antibodies completely protected human liver-uPA-SCID mice from a subsequent challenge with HCV consensus strains of different genotypes [112] . However, administration of anti-CD81 antibodies after viral challenge had no effect. Anti-SR-BI antibodies, which block the interaction of SR-BI with HCV, are another interesting strategy to prevent HCV entry. Anti-SR-BI antibodies have been demonstrated to inhibit HCVcc infection in vitro [113] . Moreover, small molecule inhibitors of SR-BI have recently been developed. For example, ITX5061 is a compound that inhibits entry of HCVpp from all major genotypes and HCVcc infection without affecting viral replication [114] . In addition, recent study demonstrated that a human monoclonal antibody targeting SR-BI efficiently precluded HCV infection and viral spread after LT in vitro and in vivo [115] . Kinetic studies suggest that this small molecule inhibitor targets HCV entry during an early postbinding stage. CLDN1 has been suggested to play an important role in cell-cell transmission. Recently, anti-CLDN1 antibodies inhibiting HCV infection in vitro have been developed [116] . The results have shown that anti-CLDN1 antibodies efficiently block cell entry of highly infectious escape variants of HCV that are resistant to host neutralizing antibodies. As mentioned above, EGFR and EphA2 are two newly established host factors for HCV entry. Thus, their respective inhibitors, erlotinib and dasatinib, are also regarded as promising HCV inhibitors in preventing HCV reinfection after LT [103] .