title: Synthesized peptide 710-725 from HCV subtype 1a E2 glycoprotein blocks HCV infection through competitive binding of CD81.
abstract: Hepatitis C virus (HCV) infection is a significant public health problem worldwide. However, there is still a lack of effective therapeutic drugs which could be used for the interruption of the disease. In the present study, for the first time, we reported that a synthesized peptide, which was synthesized by solid phase peptide synthesis and derived from the amino acids 710 to 725 of the HCV E2, functioned as an inhibitor of HCV infection. Using an MTT assay, we found that the E2 (710-725) peptide exerted no specific cytotoxicity on Huh7.5 cells and primary human hepatocytes (pHH). Interestingly, E2 (710-725) peptide blocked the entry of cell culture‑derived HCV (HCVcc) into hepatocytes. Moreover, it suppressed HCV RNA replication and HCV-specific protein NS3 and NS5B expression, as shown by western blot analysis. Moreover, E2 (710-725) markedly attenuated the inhibitory effect of HCVcc on hepatocyte viability. Additionally, a co-immunino-precipitation assay demonstrated that E2 (710-725) abrogated the interaction between CD81 and HCV E2 envelope protein through competitive binding of CD81. Overall, our results revealed that the synthesized peptide E2 (710-725) blocked CD81‑mediated HCV entry and possessed the potential to treat HCV infection. Thus, the present study provided novel insights into the development of new drugs for preventing HCV infection.
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D001667:Binding, Competitive; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology*; D060225:Tetraspanin 28 / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D010455:Peptides; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus