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World J Gastroenterol. Nov 21, 2014; 20(43): 15975-15991
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.15975
Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization
Koen Vercauteren, Ahmed Atef Mesalam, Geert Leroux-Roels, Philip Meuleman
Koen Vercauteren, Ahmed Atef Mesalam, Geert Leroux-Roels, Philip Meuleman, Center for Vaccinology, Ghent University Hospital, Ghent University, B-9000 Ghent, Belgium
Author contributions: Vercauteren K and Mesalam AA wrote the paper; Leroux-Roels G and Meuleman P critically revised it.
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; and European Union No. FP6 HEPACIVAC; FP7, HepaMab; Mesalam AA is a recipient of a PhD Fellowship provided by the Egyptian government
Correspondence to: Philip Meuleman, Professor, Center for Vaccinology, Ghent University Hospital, Ghent University, Building A, 1st floor, De Pintelaan 185, B-9000 Gent, Belgium.
Telephone: +32-9-3323658 Fax: +32-9-3326311
Received: May 28, 2014
Revised: July 9, 2014
Accepted: September 5, 2014
Published online: November 21, 2014

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.

Keywords: Hepatitis, Lipids, Neutralisation, Antiviral therapy, Animal models

Core tip: We reviewed the influence of lipids and lipoproteins on the hepatitis C virus life cycle and their impact on viral neutralization by antibodies that target the viral envelope proteins or that target the receptors used by the virus to infect the hepatocyte.