Modeling and therapy of human liver diseases using induced pluripotent stem cells: How far have we come?
✍ Scribed by Alejandro Soto-Gutierrez; Edgar Tafaleng; Victoria Kelly; Jayanta Roy-Chowdhury; Ira J. Fox
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 238 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.