Browsing by Author "Goncalves, J"
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- Attenuation of HIV-1 replication in primary human cells with a designed zinc finger transcription factorPublication . Segal, DJ; Goncalves, J; Eberhardy, S; Swan, CH; Torbett, BE; Li, XL; Barbas, CFSmall molecule inhibitors of human immunodeficiency virus, type 1 (HIV-1) have been extremely successful but are associated with a myriad of undesirable effects and require lifelong daily dosing. In this study we explore an alternative approach, that of i
- Camelized rabbit-derived VH single-domain Intrabodies Against vif strongly neutralize HIV-1 infectivityPublication . da Silva, FA; Santa-Marta, M; Freitas-Vieira, A; Mascarenhas, P; Barahona, I; Moniz-Pereira, J; Gabuzda, D; Goncalves, JWe recently developed a specific single-chain antibody from immunized rabbits to HIV-1 Vif protein that was expressed intracellularly and inhibited reverse transcription and viral replication. The Vif of HIV-1 overcomes the innate antiviral activity of a
- Catechols from abietic acidPublication . Gigante, B; Santos, C; Silva, AM; Curto, MJM; Nascimento, MSJ; Pinto, E; Pedro, M; Cerqueira, F; Pinto, MM; Duarte, MP; Laires, A; Rueff, J; Goncalves, J; Pegado, MI; Valdeira, MLCatechols from abietic acid were prepared by a short and good yielding chemical process and further evaluated for several biological activities namely, antifungal, antitumoral, antimutagenic, antiviral, antiproliferative and inhibition of nitric oxide. Their properties were compared with those of carnosic acid (6), a naturally occurring catechol with an abietane skeleton and known to possess potent antioxidant activity, as well as anticancer and antiviral properties. From all the synthetic catechols tested compound 2 showed the best activities, stronger than carnosic acid. (C) 2003 Elsevier Science Ltd. All rights reserved.
- Cell type-specific targeting with Sindbis pseudotyped lentiviral vectors displaying anti-CCR5 single-chain antibodiesPublication . Da Silva, FA; Costa, MJL; Corte-Real, S; Goncalves, JLentiviral vectors are among the most efficient tools for gene delivery into mammalian cells. A major goal of lentiviral gene delivery systems is to develop vectors that can efficiently target specific cell types. In the present work, we attempt to genera
- Different substitutions under drug pressure at protease codon 82 in HIV-1 subtype G compared to subtype B infected individuals including a novel 182M resistance mutationPublication . Camacho, R; Godinho, AR; Gomes, P; Abecasis, A; Vandamme, AM; Palma, C; Carvalho, AP; Cabanas, J; Goncalves, J
- Functional analysis of vif protein shows less restriction of human immunodeficiency virus type 2 by APOBEC3GPublication . Ribeiro, AC; Silva, AME; Silva, AME; Santa-Marta, M; Pombo, A; Moniz-Pereira, J; Goncalves, J; Barahona, IViral infectivity factor (Vif) is one of the human immunodeficiency virus (HIV) accessory proteins and is conserved in the primate lentivirus group. This protein is essential for viral replication in vivo and for productive infection of nonpermissive cell
- Functional neutralization of HIV-1 Vif protein by intracellular immunization inhibits reverse transcription and viral replicationPublication . Goncalves, J; Silva, F; Freitas-Vieira, A; Santa-Marta, M; Malho, R; Yang, XY; Gabuzda, D; Barbas, CHuman immunodeficiency virus type 1 (HIV-1)-encoded Vif protein is important for viral replication and infectivity. Vif is a cytoplasmic protein that acts during virus assembly by an unknown mechanism, enhancing viral infectivity. The action of Vif in producer cells is essential for the completion of proviral DNA synthesis following virus entry. Therefore, Vif is considered to be an important alternative therapeutic target for inhibition of viral infectivity at the level of viral assembly and reverse transcription. To gain insight into this process, we developed a Vif-specific single-chain antibody and expressed it intracellularly in the cytoplasm. This intrabody efficiently bound Vif protein and neutralized its infectivity-enhancing function. Intrabody-expressing cells were shown to be highly refractory to challenge with different strains of HIV-1 and HIV-1-infected cells. Inhibition of Vif by intrabody expression in the donor cell produced viral particles that do not complete reverse transcription in the recipient cell. The anti-Vif scFv was shown to be specific for Vif protein because its function was observed only in nonpermissive cells (H9, CEM, and U38). Moreover, transduction of peripheral blood mononuclear cells with an HIV-derived retroviral vector expressing Vif intrabody was shown to confer resistance to laboratory-adapted and primary HIV strains. This study provides biochemical evidence for the role of Vif in the HrV-1 lifecycle and validates Vif as a target for the control of HIV-1 infection.
- Functional neutralization of HIV-1 Vif protein by intracellular immunization inhibits viral replicationPublication . Goncalves, J; Silva, F; Freitas-Vieira, A; Santa-Marta, M; Malho, R; Yang, X; Gabuzda, D; Barbas, CHuman immunodeficiency virus type 1 (HIV-1) encoded Vif protein is important for viral replication and infectivity. Therefore, Vif is considered to be an important alternative therapeutic target for inhibition of viral infectivity at the level of viral as
- HIV-1 Vif can directly inhibit apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G-mediated cytidine deamination by using a single amino acid interaction and without protein degradationPublication . Santa-Marta, M; da Silva, FA; Fonseca, AM; Goncalves, JThe human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G), also known as CEM-15, is a host-cell factor involved in innate resistance to retroviral infection. HIV-1 viral infectivity factor (Vif) protein was shown to protect t
- Inhibition of human immunodeficiency virus type 1 replication with artificial transcription factors targeting the highly conserved primer-binding sitePublication . Eberhardy, SR; Goncalves, J; Coelho, S; Segal, DJ; Berkhout, B; Barbas, CFThe human immunodeficiency virus type 1 (HIV-1) primer-binding site (PBS) is a highly conserved region in the HIV genome and represents an attractive target for the development of new anti-HIV therapies. In this study, we designed four artificial zinc fin