Effect of Synthetic Peptides Belonging to E2 Envelope Protein of GB Virus C on Human Immunodeficiency Virus Type 1 Infection

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.This work was funded by Grants CTQ2006-15396-CO2-01/BQU and CTQ2009-13969-CO2-01/BQU from the Ministerio de Ciencia e Innovación, Spain. E.H. is the recipient of predoctoral grant (JAE program, CSIC, Spain). We also acknowledge Dr. Rafel Prohens (Scientific Parc of Barcelona), Dr. Ricardo Gutierrez (Pompeu Fabra University), and Dr. Julià Blanco (Fundació IRSI Caixa) for the discussion of ITC, SPR, and inhibition of cell−cell binding studies, respectively. The following reagent was obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 IIIB C34 peptide from DAIDS, NIAID.Peer reviewe

Effect of Synthetic Peptides Belonging to E2 Envelope Protein of GB Virus C on Human Immunodeficiency Virus Type 1 Infection

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.This work was funded by Grants CTQ2006-15396-CO2-01/BQU and CTQ2009-13969-CO2-01/BQU from the Ministerio de Ciencia e Innovación, Spain. E.H. is the recipient of predoctoral grant (JAE program, CSIC, Spain). We also acknowledge Dr. Rafel Prohens (Scientific Parc of Barcelona), Dr. Ricardo Gutierrez (Pompeu Fabra University), and Dr. Julià Blanco (Fundació IRSI Caixa) for the discussion of ITC, SPR, and inhibition of cell−cell binding studies, respectively. The following reagent was obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 IIIB C34 peptide from DAIDS, NIAID.Peer reviewe