Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

  • Koedel Y
  • Eissmann K
  • Wend H
  • et al.
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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.

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APA

Koedel, Y., Eissmann, K., Wend, H., Fleckenstein, B., & Reil, H. (2011). Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition. Journal of Virology, 85(14), 7037–7047. https://doi.org/10.1128/jvi.02366-10

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