摘要
Hepatitis C virus(HCV)infections represent a major global health problem.End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation.However,after transplantation the engrafted liver inevitably becomes infected by the circulating virus.Direct acting antivirals are not yet approved for use in liver transplant patients,and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting.Therefore,alternative therapeutic options need to be explored.Viral entry represents an attractive target for such therapeutic intervention.Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved.The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors.In thisreview,we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle.We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus.This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.
Hepatitis C virus (HCV) infections represent a major global health problem. End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation. However, after transplantation the engrafted liver inevitably becomes infected by the circulating virus. Direct acting antivirals are not yet approved for use in liver transplant patients, and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting. Therefore, alternative therapeutic options need to be explored. Viral entry represents an attractive target for such therapeutic intervention. Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved. The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors. In this review, we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle. We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus. This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.
基金
Supported by Ghent University,Grants No.01G00507 and No.01G01712
Research Foundation-Flanders,Projects No.1500910N,No.G0212.10N and No.G052112N(FWO-Vlaanderen)
Belgian Federal Government,No.IUAP P6/36-HEPRO and No.P7/47-HEPRO-2
European Union No.FP6 HEPACIVAC
FP7,Hepa Mab
Mesalam AA is a recipient of a PhD Fellowship provided by the Egyptian government
