5 hepatoma cells and primary hepatocytes by cell-culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16-71 in “human liver urokinase-type plasminogen activator, severe combined immune deficiency (uPA-SCID) mice” (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before viral inoculation completely protected all Selleckchem BTK inhibitor chimeric mice from infection with serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals)

suppressed the rapid viral spread

observed in untreated control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise of the viral load was observed. Conclusion: Using in vitro cell culture and human liver-chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR-BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be selleck screening library an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy. (HEPATOLOGY 2012) With approximately 3% of the world’s population infected with the hepatitis C virus (HCV), endstage liver disease caused by this infection is currently the most common indication for liver transplantation.1 However, the donor liver almost inevitably

becomes infected by circulating virus and disease progression is accelerated in immune-suppressed transplant patients.2 Less than 30% of liver transplant patients treated with pegylated interferon therapy with or without ribavirin will achieve a sustained virological response and this combination therapy is often not well tolerated.3-5 selleck chemicals Therefore, new strategies to prevent graft reinfection are urgently needed. In the coming years, new direct antiviral compounds will considerably improve therapy outcome in patients without severe liver disease,6-8 but the side effects and potential drug-drug interactions associated with triple therapy may severely complicate their use in liver transplant patients with endstage liver disease.9-12 Because of the extreme genetic diversity of HCV and its ability to spread by way of cell-cell contacts, successful immunotherapy with polyclonal or monoclonal HCV-specific antibodies may be difficult to achieve.13-17 In contrast, viral (co-)receptors are genetically conserved and may represent better therapeutic targets. HCV entry is a multistep process in which different putative attachment factors and viral receptors are involved (reviewed18-20).