أعرض تسجيلة المادة بشكل مبسط

dc.creator Real, Gustavo del
dc.creator Jiménez Baranda, Sonia
dc.creator Mira, Emilia
dc.creator Lacalle, Rosa Ana
dc.creator Lucas, Pilar
dc.creator Gómez-Moutón, Concepción
dc.creator Alegret, Marta
dc.creator Peña, José María
dc.creator Rodríguez Zapata, Manuel
dc.creator Álvarez-Mon, Melchor
dc.creator Martínez-Alonso, Carlos
dc.creator Mañes, Santos
dc.date 2008-03-27T08:01:58Z
dc.date 2008-03-27T08:01:58Z
dc.date 2004-08
dc.date.accessioned 2017-01-31T01:00:57Z
dc.date.available 2017-01-31T01:00:57Z
dc.identifier The Journal of Experimental Medicine, volume 200, number 4, august 16, 2004, pp. 541–547
dc.identifier 0022-1007
dc.identifier http://hdl.handle.net/10261/3323
dc.identifier doi/10.1084/jem.20040061
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3323
dc.description Copyright © by The Rockefeller University Press
dc.description 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.
dc.description Peer reviewed
dc.format 861610 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.rights openAccess
dc.subject Cholesterol
dc.subject Actin cytoskeleton
dc.subject Small GTPases
dc.subject Lipid rafts
dc.subject Prenylation
dc.title Statins Inhibit HIV-1 infection by down-regulating rho activity
dc.type Artículo


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أعرض تسجيلة المادة بشكل مبسط