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Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity
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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
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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. Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity. _Journal of Experimental Medicine_. 2004. Vol. 200, núm. 4, pàgs. 541-547. [consulta: 25 de febrer de 2026]. ISSN: 0022-1007. [Disponible a: https://hdl.handle.net/2445/130338]