title: Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes.
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.
  
  
  CONCLUSIONS
  Together, the results suggested an association between HCV E1 and apolipoproteins, which may facilitate virus entry through LDL-R into mammalian cells.
authors: Department of Internal Medicine, St. Louis University, St. Louis, MO, USA.
authors: Budhaditya
authors: B
authors: Mazumdar
authors: Arup
authors: A
authors: Banerjee
authors: Keith
authors: K
authors: Meyer
authors: Ranjit
authors: R
authors: Ray
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D010978:Platelet Factor 4 / Q000494:pharmacology; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011817:Rabbits; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D001053:Apolipoproteins; C087035:E1 protein, Hepatitis C virus; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D014759:Viral Envelope Proteins; D010978:Platelet Factor 4; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases