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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3323| Title: | Statins Inhibit HIV-1 infection by down-regulating rho activity |
| Keywords: | Cholesterol Actin cytoskeleton Small GTPases Lipid rafts Prenylation |
| Publisher: | Rockefeller University Press |
| Description: | Copyright © by The Rockefeller University Press 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. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3323 |
| Other Identifiers: | The Journal of Experimental Medicine, volume 200, number 4, august 16, 2004, pp. 541–547 0022-1007 http://hdl.handle.net/10261/3323 doi/10.1084/jem.20040061 |
| Appears in Collections: | Digital Csic |
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