Effects of the Mammalian Target of Rapamycin Inhibitor Everolimus on Hepatitis C Virus Replication In Vitro and In Vivo.

摘要: Abstract Background The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target rapamycin inhibitors, remains unclear. aim our study was to analyze the everolimus (EVR) HCV replication activity in context underlying molecular mechanisms, with focus pro-myelocytic leukemia protein (PML). Methods viral load recorded 40 patients post-transplant before and 8 weeks introduction EVR. An cell culture replicon system for genotype (GT) 1b, GT2b, GT3a used compare EVR respective genotypes in vitro. Fluorescence-activated cell-sorting analysis test effects proliferation. PML expression silenced use small hairpin RNA constructs, quantified by means quantitative real-time polymerase chain reaction. Results In HCV, GT1a GT1b hardly affected EVR, whereas reduced GT2a (P ≤ .0001) or GT3 infection .05). vitro impairs up 60% .0005), cells, is increased 50% .005). Replicon viability not impaired. impaired absence PML, which can be reversed overexpression isoforms. Furthermore, effect nearly abrogated. Conclusions inhibitor influences via PML. herein presented results suggest a genotype-dependent benefit an EVR-based immunosuppressive regimen transplantation.