Article first published online: 2 JUL 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 2, pages 484–491, August 2012
How to Cite
Liu, S., McCormick, K. D., Zhao, W., Zhao, T., Fan, D. and Wang, T. (2012), Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding. Hepatology, 56: 484–491. doi: 10.1002/hep.25665
Potential conflict of interest: Nothing to report.
Supported by the National Institutes of Health (NIH), grants NIH R21AI083389 (to T.W.); NIH R01DK088787 (to T.W.); NIH R21HL106325 (to D.F.).
- Issue published online: 25 JUL 2012
- Article first published online: 2 JUL 2012
- Accepted manuscript online: 15 FEB 2012 04:10AM EST
- Manuscript Accepted: 9 FEB 2012
- Manuscript Received: 6 SEP 2011
Hepatitis C virus (HCV) entry is a multiple-step process involving a number of host factors and hence represents a promising target for new antiviral drug development. In search of novel inhibitors of HCV infection, we found that a human apolipoprotein E (apoE) peptide, hEP, containing both a receptor binding fragment and a lipid binding fragment of apoE specifically blocked the entry of cell culture grown HCV (HCVcc) at submicromolar concentrations. hEP caused little cytotoxicity in vitro and remained active even if left 24 hours in cell culture. Interestingly, hEP inhibited neither human immunodeficiency virus (HIV)-HCV pseudotypes (HCVpp) nor HIV and Dengue virus (DENV) infection. Further characterization mapped the anti-HCV activity to a 32-residue region that harbors the receptor binding domain of apoE, but this fragment must contain a cysteine residue at the N-terminus to mediate dimer formation. The anti-HCV activity of the peptide appears to be dependent on both its length and sequence and correlates with its ability to bind lipids. Finally, we demonstrated that the apoE-derived peptides directly blocked the binding of both HCVcc and patient serum-derived virus to hepatoma cells as well as primary human hepatocytes. Conclusion: apoE peptides potently inhibit HCV infection and suggest a direct role of apoE in mediating HCV entry. Our findings also highlight the potential of developing apoE mimetic peptides as novel HCV entry inhibitors by targeting HCV-host interactions. (HEPATOLOGY 2012)