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http://hdl.handle.net/2445/130338
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DC Field | Value | Language |
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dc.contributor.author | Del Real, Gustavo | - |
dc.contributor.author | Jiménez-Baranda, Sonia | - |
dc.contributor.author | Mira, Emilia | - |
dc.contributor.author | Lacalle, Rosa Ana | - |
dc.contributor.author | Lucas, Pilar | - |
dc.contributor.author | Gómez-Moutón, Concepción | - |
dc.contributor.author | Alegret i Jordà, Marta | - |
dc.contributor.author | Peña, Jose M. | - |
dc.contributor.author | Rodriguez-Zapata, Manuel | - |
dc.contributor.author | Alvarez-Mon, Melchor | - |
dc.contributor.author | Martinez-A., Carlos | - |
dc.contributor.author | Mañes, Santos | - |
dc.date.accessioned | 2019-03-14T08:28:03Z | - |
dc.date.available | 2019-03-14T08:28:03Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/2445/130338 | - |
dc.description.abstract | Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft-associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. Rho GTPase activity can be negatively regulated by statins, a family of drugs used to treat hypercholesterolemia in man. Statins mediate inhibition of Rho GTPases by impeding prenylation of small G proteins through blockade of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show that statins decreased viral load and increased CD4+ cell counts in acute infection models and in chronically HIV-1-infected patients. Viral entry and exit was reduced in statin-treated cells, and inhibition was blocked by the addition of l-mevalonate or of geranylgeranylpyrophosphate, but not by cholesterol. Cell treatment with a geranylgeranyl transferase inhibitor, but not a farnesyl transferase inhibitor, specifically inhibited entry of HIV-1-pseudotyped viruses. Statins blocked Rho-A activation induced by HIV-1 binding to target cells, and expression of the dominant negative mutant RhoN19 inhibited HIV-1 envelope fusion with target cell membranes, reducing cell infection rates. We suggest that statins have direct anti-HIV-1 effects by targeting Rho. Keywords: cholesterol, actin cytoskeleton, small GTPases, lipid rafts, prenylation | - |
dc.format.extent | 7 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Rockefeller University Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1084/jem.20040061 | - |
dc.relation.ispartof | Journal of Experimental Medicine, 2004, vol. 200, num. 4, p. 541-547 | - |
dc.relation.uri | https://doi.org/10.1084/jem.20040061 | - |
dc.rights | (c) Rockefeller University Press, 2004 | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Colesterol | - |
dc.subject.classification | Proteïnes citosquelètiques | - |
dc.subject.classification | Proteïnes de membrana | - |
dc.subject.classification | VIH (Virus) | - |
dc.subject.other | Cholesterol | - |
dc.subject.other | Cytoskeletal proteins | - |
dc.subject.other | Membrane proteins | - |
dc.subject.other | HIV (Viruses) | - |
dc.title | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 519103 | - |
dc.date.updated | 2019-03-14T08:28:03Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 15314078 | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
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519103.pdf | 845.57 kB | Adobe PDF | View/Open |
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