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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Xia
Wei-Liang
WL
Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Shen
Yan
Y
Zheng
Shu-Sen
SS
D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014779:Virus Replication / Q000187:drug effects*
D016572:Cyclosporine