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Hospital de Órbigo, Spain

Gomara M.J.,CSIC - Institute of Advanced Chemistry of Catalonia | Sanchez-Merino V.,Institute dInvestigacions Biomediques August Pi i Sunyer | Paus A.,CSIC - Institute of Advanced Chemistry of Catalonia | Merino-Mansilla A.,Institute dInvestigacions Biomediques August Pi i Sunyer | And 4 more authors.
Biochimica et Biophysica Acta - General Subjects | Year: 2016

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. © 2016 Elsevier B.V. All rights reserved.

Gomara M.J.,CSIC - Institute of Advanced Chemistry of Catalonia | Galatola R.,CSIC - Institute of Advanced Chemistry of Catalonia | Gutierrez A.,Institute Sintesis Quimica y Catalisis Homogenea ISQCH CSIC | Gimeno M.C.,Institute Sintesis Quimica y Catalisis Homogenea ISQCH CSIC | And 4 more authors.
Current Medicinal Chemistry | Year: 2014

Following the report of beneficial effects of co-infection by GB virus C (GBV-C) for HIV-infected patients, we have studied synthetic GBV-C peptides and their relationship with HIV type-1. This paper reports the design and synthesis of new forms of presentation of two peptide inhibitors corresponding to the envelope proteins E1 and E2 of GBV-C, together with a study of their anti-HIV-1 activity. Homogeneous and heterogeneous multiple antigenic peptides (MAPs), lipophilic derivatizations, cyclization and peptide-gold conjugations are the chemical design strategies adopted. Our aim is to enhance the anti-viral potency of the GBV-C peptide domains. Of all the GBV-C peptide derivatives studied, peptide- gold complexes derived from the (22-39) sequence of the GBV-C E1 protein were the most active entry inhibitors. These results support the putative modulation of HIV-1 infection by the GBV-C E1 protein and open new perspectives for the development of novel peptide-derived HIV-1 entry inhibitors. © 2014 Bentham Science Publishers.

Sanchez-Palomino S.,Infectious Diseases Unit HIVACAT | Massanella M.,Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Carrillo J.,Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Garcia A.,Infectious Diseases Unit HIVACAT | And 10 more authors.
Vaccine | Year: 2011

Background: Cell-to-cell HIV spread through virological synapses proceeds in two steps, first HIV particles are rapidly transferred to target cells in a CD4-dependent manner and then coreceptor-dependent events allow for infection or death of single target cells and cell-to-cell fusion. Methods: 293T or MOLT cells producing HIV particles were cocultured with primary CD4 T-cells or reporter cell lines. The extent of HIV transfer, cell fusion and target cell death was assessed. Inhibition by sera from 19 HIV-infected patients was evaluated and compared with cell-free HIV neutralization using different envelopes from clades A, B, C and E. Results: Sera showed different abilities to protect CD4 T-cells from cell-to-cell transfer, fusion or death when cocultured with HIV producing 293T cells. Some sera were able to block all parameters (a property of IgGb12), while other showed lower activity against HIV transfer despite being able to block fusion and death (a property of antibodies blocking post-CD4 binding steps). Neutralization of cell-to-cell HIV transfer strongly correlated with IgG binding to native Env. Interestingly, sera that efficiently blocked HIV transfer showed broader neutralizing response, as they neutralized a higher percentage of the viruses tested compared with sera showing low CD4 binding site responses (P= 0.01). Similar results were observed in a model of T cell-T cell HIV transmission, although this experimental model showed lower capacity to discriminate broadly neutralizing responses. Conclusion: Cell-to-cell HIV transfer assays identify sera with broadly neutralizing capacity and may help to characterize anti-HIV humoral responses. © 2011 Elsevier Ltd.

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