title: Synthesized peptides 705-734 from hepatitis C virus E2 glycoprotein induce dendritic cell maturation by activating p38 MAPK signaling.
abstract: Hepatitis C virus (HCV) envelope E2 is a glycoprotein that are implicated in HCV infection by facilitating its entry and immune evasion, which in turn leads to hepatitis, hepatocellular carcinoma and other chronic liver diseases. It is reported that the HCV E2 stem region comprise a functional region for HCV entry; however, the roles and underlying mechanism of these conserved residues on the E2 protein in the immune response after HCV infection are still not well defined. In this study, we synthesized 30 aa peptides containing residues 705-734 (E2-705) of HCV E2 using the solid-phase peptide synthesis (SPPS) method. The characteristics of the synthesized peptides were identified by Western blot and cell culture derived HCV particles (HCVcc) infection blocking assay. ELISA and flow cytometry assays were employed to determine the effect of the synthesized peptide on dendritic cells (DCs) response and CD4(+) T cell activation. Results showed that the synthesized E2-705 peptides binds to DCs by interaction with DC-SIGN receptor. E2-705 peptides induced the maturation of infected DCs to a similar extent with recombinant HCV E2 as reflected by the antigen uptake potential and allostimulatory capacity. Furthermore, the E2-705 peptides increased the production of IL-12, CD80 and CD86 but reduced the IL-10 in DCs, in which p38 MAPK signaling might be involved. These results suggest that the carboxyl-terminus beyond the core ectodomain of HCV E2 protein may play a key role in immunoreaction of HCV infection, giving a new understanding of HCV E2 and a novel target for the design of HCV vaccines or inhibitors.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. Electronic address: shumeilinxa@163.com.
authors.forename: Shumei
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. Electronic address: minliusx@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000737:chemistry; D014761:Viral Hepatitis Vaccines / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016753:Interleukin-10; D018664:Interleukin-12; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C091015:glycoprotein E2, Hepatitis C virus
keywords: Dendritic cell; HCV E2-705-734 peptides; Immune evasion; Maturation; p38 MAPK