Definition of an 18-mer Synthetic Peptide Derived from the GB virus C E1 Protein as a New HIV-1 Entry Inhibitor

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 El protein in HIV-1 inhibition. Methods: The present work involves the construction of several overlapping peptide libraries scanning the GBV-C El 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. General Significance: 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. (C) 2016 Elsevier B.V. All rights reserved.