New Insights in Recurrent HCV Infection after Liver Transplantation

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

Rapamycin. With low nephrotoxicity and potential anticancer properties, rapamycin has been increasingly used in the transplantation context [47] . It has been well known that rapamycin engages the cytosolic protein FKBP12 to form a complex. This complex inhibits the mTOR pathway by directly binding to the mTOR complex 1, resulting in blockage of cell cycle progression from the G1 to S phase and thereby causing inhibition of T cell proliferation. Intriguingly, rapamycin induces autophagy through inhibiting mTOR. Autophagy is a process for catabolizing organelles and other intracellular components to balance cellular metabolism and to promote cell survival during stressful conditions. In fact, autophagy is also an important event in the regulation of the cellular response against viral infections [48] . It is noteworthy that HCV infection induces autophagy in the hepatocytes via the unfolded protein response, and the autophagy induced by HCV is incomplete through blocking the maturation of autophagosomes to autolysosomes [49] . The autophagosomes will not be degraded but instead support viral replication. Recent study demonstrated that NS5B could directly interact with the host proteins to induce the autophagy [50] . In addition, the HCV-induced autophagy may promote infection by reducing the innate immunity [51] . Based on these findings, it is conceivable that rapamycin could affect HCV recurrence and antiviral interferon therapy. However, clinical evidence is needed to make sure of its in vivo effect.