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Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity
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 trea...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211926/ https://www.ncbi.nlm.nih.gov/pubmed/15314078 http://dx.doi.org/10.1084/jem.20040061 |
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author | del Real, Gustavo Jiménez-Baranda, Sonia Mira, Emilia Lacalle, Rosa Ana Lucas, Pilar Gómez-Moutón, Concepción Alegret, Marta Peña, Jose María Rodríguez-Zapata, Manuel Alvarez-Mon, Melchor Martínez-A., Carlos Mañes, Santos |
author_facet | del Real, Gustavo Jiménez-Baranda, Sonia Mira, Emilia Lacalle, Rosa Ana Lucas, Pilar Gómez-Moutón, Concepción Alegret, Marta Peña, Jose María Rodríguez-Zapata, Manuel Alvarez-Mon, Melchor Martínez-A., Carlos Mañes, Santos |
author_sort | del Real, Gustavo |
collection | PubMed |
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. |
format | Text |
id | pubmed-2211926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22119262008-03-11 Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity del Real, Gustavo Jiménez-Baranda, Sonia Mira, Emilia Lacalle, Rosa Ana Lucas, Pilar Gómez-Moutón, Concepción Alegret, Marta Peña, Jose María Rodríguez-Zapata, Manuel Alvarez-Mon, Melchor Martínez-A., Carlos Mañes, Santos J Exp Med Brief Definitive Report 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. The Rockefeller University Press 2004-08-16 /pmc/articles/PMC2211926/ /pubmed/15314078 http://dx.doi.org/10.1084/jem.20040061 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report del Real, Gustavo Jiménez-Baranda, Sonia Mira, Emilia Lacalle, Rosa Ana Lucas, Pilar Gómez-Moutón, Concepción Alegret, Marta Peña, Jose María Rodríguez-Zapata, Manuel Alvarez-Mon, Melchor Martínez-A., Carlos Mañes, Santos Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title_full | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title_fullStr | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title_full_unstemmed | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title_short | Statins Inhibit HIV-1 Infection by Down-regulating Rho Activity |
title_sort | statins inhibit hiv-1 infection by down-regulating rho activity |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211926/ https://www.ncbi.nlm.nih.gov/pubmed/15314078 http://dx.doi.org/10.1084/jem.20040061 |
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