Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and its possible mechanisms.

Abstract Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT). However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in China. Cyclosporine A (CsA), which is routinely used to prevent the allograft rejection, is reported to have the inhibitory activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possible mechanisms of CsA on HBV replication in vitro. An English-language literature search was conducted using MEDLINE (1990-2004) on cyclosporine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles. Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cyclophilin D, then blocking the mitochondria-mediated cytosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro. By interacting with mitochondria, preventing the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.