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Please use this identifier to cite or link to this item: http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3323
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dc.creatorReal, Gustavo del-
dc.creatorJiménez Baranda, Sonia-
dc.creatorMira, Emilia-
dc.creatorLacalle, Rosa Ana-
dc.creatorLucas, Pilar-
dc.creatorGómez-Moutón, Concepción-
dc.creatorAlegret, Marta-
dc.creatorPeña, José María-
dc.creatorRodríguez Zapata, Manuel-
dc.creatorÁlvarez-Mon, Melchor-
dc.creatorMartínez-Alonso, Carlos-
dc.creatorMañes, Santos-
dc.date2008-03-27T08:01:58Z-
dc.date2008-03-27T08:01:58Z-
dc.date2004-08-
dc.date.accessioned2017-01-31T01:00:57Z-
dc.date.available2017-01-31T01:00:57Z-
dc.identifierThe Journal of Experimental Medicine, volume 200, number 4, august 16, 2004, pp. 541–547-
dc.identifier0022-1007-
dc.identifierhttp://hdl.handle.net/10261/3323-
dc.identifierdoi/10.1084/jem.20040061-
dc.identifier.urihttp://dspace.mediu.edu.my:8181/xmlui/handle/10261/3323-
dc.descriptionCopyright © by The Rockefeller University Press-
dc.descriptionHuman 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.-
dc.descriptionPeer reviewed-
dc.format861610 bytes-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherRockefeller University Press-
dc.rightsopenAccess-
dc.subjectCholesterol-
dc.subjectActin cytoskeleton-
dc.subjectSmall GTPases-
dc.subjectLipid rafts-
dc.subjectPrenylation-
dc.titleStatins Inhibit HIV-1 infection by down-regulating rho activity-
dc.typeArtículo-
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