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

• Published in: Biochimica et biophysica acta Vol. 1860; no. 6; pp. 1139 - 1148
• Main Authors: Gómara, M.J., Sánchez-Merino, V., Paús, A., Merino-Mansilla, A., Gatell, J.M., Yuste, E., Haro, I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2016
• Subjects: Amino Acid Sequence; Anti-HIV Agents - pharmacology; antiretroviral agents; antiviral properties; E1 protein; energy transfer; entry inhibitor; enzyme-linked immunosorbent assay; fluorescence; fusion peptide; GB virus C; hemolysis; Hepatitis GB virus B; HIV-1; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus 1; Molecular Sequence Data; mortality; Peptide Fragments - pharmacology; peptide libraries; synthetic peptide; synthetic peptides; Viral Envelope Proteins - pharmacology; viremia; Virus Internalization - drug effects; viruses; HIV-1; fusion peptide; OPD; FP; HT; NBD; POPG; GBV-C; Rho; HATU; Dbz; synthetic peptide; entry inhibitor; DIPEA; MPAA; Nbz; Pmc; GB virus C; Acm; ACN; LUV; mAb; SEC; E1 protein; MPER; NCL; VIRIP; VSV; HB; TCEP; DHB; HAART; TIS
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.02.008

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. 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. [Display omitted] •E1 GBV-C protein is a source of peptides for the development of anti-HIV therapies•E1P47 shows antiviral activity against HIV-1 viruses from clades A, B, C, D and AE•The E1P47 peptide interacts with the HIV-1 Fusion Peptide