title: Definition of an 18-mer Synthetic Peptide Derived from the GB virus C E1 Protein as a New HIV-1 Entry Inhibitor.
abstract: BACKGROUND
  A slower progression of AIDS and increased survival in GBV-C positive individuals, compared with GBV-C negative individuals has been demonstrated; while the loss of GBV-C viremia was closely associated with a rise in mortality and increased progression of AIDS. Following on from the previous reported studies that support the thesis that GBV-C E2 interferes with HIV-1 entry, in this work we try to determine the role of the GBV-C E1 protein in HIV-1 inhibition.
  
  
  METHODS
  The present work involves the construction of several overlapping peptide libraries scanning the GBV-C E1 protein and the evaluation of their anti-HIV activity.
  
  
  RESULTS
  Specifically, an 18-mer synthetic peptide from the GBV-C E1 protein, E1(139-156), showed similar antiviral activity against HIVs from viruses from clades A, B, C, D and AE. Competitive ELISA using specific gp41-targeting mAbs, fluorescence resonance energy transfer as well as haemolysis assays demonstrated that this E1 peptide sequence interacts with the highly conserved N-terminal region of the HIV-1 gp41 (the fusion peptide) which is essential for viral entry.
  
  
  CONCLUSIONS
  We have defined a novel peptide lead compound and described the inhibitory role of a highly conserved fragment of the E1 protein.
  
  
  CONCLUSIONS
  The results together allow us to consider the non-pathogenic E1 GBV-C protein as an attractive source of peptides for the development of novel anti-HIV therapies.
authors.affiliation: Unit of Synthesis and Biomedical Application of Peptides. IQAC-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain. Electronic address: mariajose.gomara@iqac.csic.es.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gómara
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain. HIVACAT, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Sánchez-Merino
authors.affiliation: Unit of Synthesis and Biomedical Application of Peptides. IQAC-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Paús
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain. HIVACAT, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Merino-Mansilla
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain. HIVACAT, Barcelona, Spain; Infectious Diseases Unit-HIVACAT, Hospital Clinic, Villarroel, 170, 08036 Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain. HIVACAT, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Yuste
authors.affiliation: Unit of Synthesis and Biomedical Application of Peptides. IQAC-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain. Electronic address: isabel.haro@iqac.csic.es.
authors.forename: I
authors.initials: I
authors.lastname: Haro
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C114224:envelope protein E1, GB virus C
keywords: E1 protein; GB virus C; HIV-1; entry inhibitor; fusion peptide; synthetic peptide