| 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 |
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| 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 |
|