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Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery

To accomplish their life cycle, lentiviruses make use of host proteins, the so-called cellular cofactors. Interactions between host cell and viral proteins during early stages of lentiviral infection provide attractive new antiviral targets. The insertion of lentiviral cDNA in a host cell chromosome...

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Autores principales: Taltynov, Oliver, Desimmie, Belete A., Demeulemeester, Jonas, Christ, Frauke, Debyser, Zeger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420096/
https://www.ncbi.nlm.nih.gov/pubmed/22928108
http://dx.doi.org/10.1155/2012/863405
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author Taltynov, Oliver
Desimmie, Belete A.
Demeulemeester, Jonas
Christ, Frauke
Debyser, Zeger
author_facet Taltynov, Oliver
Desimmie, Belete A.
Demeulemeester, Jonas
Christ, Frauke
Debyser, Zeger
author_sort Taltynov, Oliver
collection PubMed
description To accomplish their life cycle, lentiviruses make use of host proteins, the so-called cellular cofactors. Interactions between host cell and viral proteins during early stages of lentiviral infection provide attractive new antiviral targets. The insertion of lentiviral cDNA in a host cell chromosome is a step of no return in the replication cycle, after which the host cell becomes a permanent carrier of the viral genome and a producer of lentiviral progeny. Integration is carried out by integrase (IN), an enzyme playing also an important role during nuclear import. Plenty of cellular cofactors of HIV-1 IN have been proposed. To date, the lens epithelium-derived growth factor (LEDGF/p75) is the best studied cofactor of HIV-1 IN. Moreover, small molecules that block the LEDGF/p75-IN interaction have recently been developed for the treatment of HIV infection. The nuclear import factor transportin-SR2 (TRN-SR2) has been proposed as another interactor of HIV IN-mediating nuclear import of the virus. Using both proteins as examples, we will describe approaches to be taken to identify and validate novel cofactors as new antiviral targets. Finally, we will highlight recent advances in the design and the development of small-molecule inhibitors binding to the LEDGF/p75-binding pocket in IN (LEDGINs).
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spelling pubmed-34200962012-08-27 Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery Taltynov, Oliver Desimmie, Belete A. Demeulemeester, Jonas Christ, Frauke Debyser, Zeger Mol Biol Int Review Article To accomplish their life cycle, lentiviruses make use of host proteins, the so-called cellular cofactors. Interactions between host cell and viral proteins during early stages of lentiviral infection provide attractive new antiviral targets. The insertion of lentiviral cDNA in a host cell chromosome is a step of no return in the replication cycle, after which the host cell becomes a permanent carrier of the viral genome and a producer of lentiviral progeny. Integration is carried out by integrase (IN), an enzyme playing also an important role during nuclear import. Plenty of cellular cofactors of HIV-1 IN have been proposed. To date, the lens epithelium-derived growth factor (LEDGF/p75) is the best studied cofactor of HIV-1 IN. Moreover, small molecules that block the LEDGF/p75-IN interaction have recently been developed for the treatment of HIV infection. The nuclear import factor transportin-SR2 (TRN-SR2) has been proposed as another interactor of HIV IN-mediating nuclear import of the virus. Using both proteins as examples, we will describe approaches to be taken to identify and validate novel cofactors as new antiviral targets. Finally, we will highlight recent advances in the design and the development of small-molecule inhibitors binding to the LEDGF/p75-binding pocket in IN (LEDGINs). Hindawi Publishing Corporation 2012 2012-08-07 /pmc/articles/PMC3420096/ /pubmed/22928108 http://dx.doi.org/10.1155/2012/863405 Text en Copyright © 2012 Oliver Taltynov et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Taltynov, Oliver
Desimmie, Belete A.
Demeulemeester, Jonas
Christ, Frauke
Debyser, Zeger
Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title_full Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title_fullStr Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title_full_unstemmed Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title_short Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
title_sort cellular cofactors of lentiviral integrase: from target validation to drug discovery
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420096/
https://www.ncbi.nlm.nih.gov/pubmed/22928108
http://dx.doi.org/10.1155/2012/863405
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