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http://hdl.handle.net/2445/130338
Title: | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
Author: | Del Real, Gustavo Jiménez-Baranda, Sonia Mira, Emilia Lacalle, Rosa Ana Lucas, Pilar Gómez-Moutón, Concepción Alegret i Jordà, Marta Peña, Jose M. Rodriguez-Zapata, Manuel Alvarez-Mon, Melchor Martinez-A., Carlos Mañes, Santos |
Keywords: | Colesterol Proteïnes citosquelètiques Proteïnes de membrana VIH (Virus) Cholesterol Cytoskeletal proteins Membrane proteins HIV (Viruses) |
Issue Date: | 2004 |
Publisher: | Rockefeller University Press |
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 |
Note: | Reproducció del document publicat a: https://doi.org/10.1084/jem.20040061 |
It is part of: | Journal of Experimental Medicine, 2004, vol. 200, num. 4, p. 541-547 |
URI: | http://hdl.handle.net/2445/130338 |
Related resource: | https://doi.org/10.1084/jem.20040061 |
ISSN: | 0022-1007 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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