Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes
Open Access
- 6 July 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 54 (4), 1149-1156
- https://doi.org/10.1002/hep.24523
Abstract
Our previous studies demonstrated that hepatitis C virus (HCV) envelope glycoproteins 1 and 2 (E1 and E2) display distinct reactivity to different cell‐surface molecules. In this study, we characterized the interaction of E1 and E2 with apolipoproteins in facilitating virus entry. The results suggested a higher neutralization of vesicular stomatitis virus (VSV)/HCV E1‐G pseudotype infectivity by antibodies to apolipoprotein E (ApoE) than apolipoprotein B (ApoB), with VSV/HCV E2‐G pseudotype infectivity remaining largely unaffected. Neutralization of cell‐culture–grown HCV infectivity by antiserum to ApoE and, to a lesser extent, by ApoB further verified their involvement in virus entry. HCV E1, but not E2, displayed binding with ApoE and ApoB by enzyme‐linked immunosorbent assay. Binding of E1 with apolipoproteins were further supported by coimmunoprecipitation from human hepatocytes expressing E1. Rabbit antiserum to a selected E1 ectodomain‐derived peptide displayed ∼50% neutralization of E1‐G pseudotype infectivity. Furthermore, E1 ectodomain‐derived synthetic peptides significantly inhibited the interaction of E1 with both the apolipoproteins. Investigation on the role of low‐density lipoprotein receptor (LDL‐R) as a hepatocyte surface receptor for virus entry suggested a significant reduction in E1‐G pseudotype plaque numbers (∼70%) by inhibiting LDL‐R ligand‐binding activity using human proprotein convertase subtilisin/kexin type 9 and platelet factor‐4, whereas they had a minimal inhibitory effect on the E2‐G pseudotype. Conclusion: Together, the results suggested an association between HCV E1 and apolipoproteins, which may facilitate virus entry through LDL‐R into mammalian cells. (HEPATOLOGY 2011;)This publication has 35 references indexed in Scilit:
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