| Activation of Latent HIV-1 Expression by Protein Kinase C Agonists. A Novel Therapeutic Approach to Eradicate HIV-1 Reservoirs. | |
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MedLine Citation:
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PMID: 20955147 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy. The molecular mechanisms by which integrated HIV-1 is repressed during latency have been partially identified in different models of HIV-1 latency, and the involvement of multiple processes has been demonstrated. Therefore, several molecular targets amenable to pharmacological manipulation have emerged to antagonize HIV-1 latency in the viral reservoirs. In this context, it has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harbouring latent HIV-1 provirus. HIV-1 reactivation therapy is a potential therapeutic option to purge the viral reservoirs. The goal of this therapy is to enhance the transcriptional activity of the latent HIV-1 without inducing the polyclonal activation of non-infected cells. In this sense natural or semisynthetic protein kinase C agonists lacking tumour-promoter activities clearly fulfil this criterion, thereby opening new research avenues to purge HIV-1 reservoirs. In this review article, we have succinctly summarized the known effects of "natural products", focusing on phorboids like prostratin and ingenols, macrolides like bryostatin 1, and macrocyclic polyesters like ingols and jatrophanes. A comprehensive view on the molecular mechanisms underlying the principle of HIV-1 reactivation from latency is provided, discussing the combination of "natural products" with other experimental or conventional therapeutics. |
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Authors:
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Gonzalo Sánchez-Duffhues; Minh Q Vo; Moisés Pérez; Marco A Calzado; Santiago Moreno; Giovanni Appendino; Eduardo Muñoz |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Current drug targets Volume: 12 ISSN: 1873-5592 ISO Abbreviation: Curr Drug Targets Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100960531 Medline TA: Curr Drug Targets Country: Netherlands |
Other Details:
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Languages: eng Pagination: 348-56 Citation Subset: IM |
Affiliation:
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Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Medicina. Avda. de Menendez Pidal s/n, 14004, Universidad de Córdoba, Spain. fi1muble@uco.es. |
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