Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Fitxers

519103.pdf (845.57 KB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2004

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/130338

Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1084/jem.20040061

Resum

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

Matèries

Colesterol, Proteïnes citosquelètiques, Proteïnes de membrana, VIH (Virus)

Matèries (anglès)

Cholesterol, Cytoskeletal proteins, Membrane proteins, HIV (Viruses)

Citació

Col·leccions

Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citació

DEL REAL, Gustavo, et al. Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity. Journal of Experimental Medicine. 2004. Vol. 200, num. 4, pags. 541-547. ISSN 0022-1007. [consulted: 20 of August of 2026]. Available at: https://hdl.handle.net/2445/130338

Exportar metadades

JSON - METS

Compartir registre