title: Peptides derived from a distinct region of GB virus C glycoprotein E2 mediate strain-specific HIV-1 entry inhibition.
abstract: The nonpathogenic human GB virus C (GBV-C), a member of the Flaviviridae, is highly prevalent in individuals with HIV-1 infections or with parenteral and sexual risk factors. Long-term GBV-C viremia has been associated with better survival or improved diagnosis in several epidemiological studies. In a previous study we reported that the E2 glycoprotein of GBV-C interferes with HIV-1 entry in vitro. To address the question what region of the E2 protein is involved in suppression of HIV-1 replication, we performed an E2-derived peptide scanning and determined the HIV-inhibitory activity of each peptide in HIV replication assays. We demonstrate here that peptides representing the N-terminal part of the E2 protein from amino acids (aa) 29 to 72 are able to inhibit efficiently HIV-1 replication in vitro. In particular, the peptides P6-2 (representing the E2-region from aa 45 to 64) and P4762 (aa 37 to 64) showed the highest potency in HIV replication assays performed on TZM-bl cells with 50% inhibitory concentrations between 0.1 and 2 μM. However, primary HIV-1 isolates representing clades A to H showed a high variability in their sensitivity to E2 peptides. Pseudovirus inhibition assays revealed that the sensitivity is determined by the gp120/gp41 envelope proteins. Using HIV-1 BlaM-Vpr-based fusion assays, we demonstrate that the E2-derived peptides prevent HIV-1 binding or fusion, presumably via interaction with the HIV-1 particle. Together, these findings reveal a new mechanism of viral interference, suggesting that the envelope protein E2 of GBV-C target directly HIV-1 particles to avoid entry of these virions.
authors.affiliation: Institute for Virology, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Koedel
authors.forename: Kristin
authors.initials: K
authors.lastname: Eissmann
authors.forename: Holger
authors.initials: H
authors.lastname: Wend
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: Heide
authors.initials: H
authors.lastname: Reil
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D029407:GB virus C / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D010455:Peptides; D014759:Viral Envelope Proteins; C107619:glycoprotein E2, GB virus C