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In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4

BACKGROUND: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immun...

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Autores principales: Higuita, Edwin A, Jaimes, Fabián A, Rugeles, Maria T, Montoya, Carlos J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668251/
https://www.ncbi.nlm.nih.gov/pubmed/23634877
http://dx.doi.org/10.1186/1742-6405-10-10
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author Higuita, Edwin A
Jaimes, Fabián A
Rugeles, Maria T
Montoya, Carlos J
author_facet Higuita, Edwin A
Jaimes, Fabián A
Rugeles, Maria T
Montoya, Carlos J
author_sort Higuita, Edwin A
collection PubMed
description BACKGROUND: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. METHODS: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. RESULTS: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. CONCLUSIONS: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains.
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spelling pubmed-36682512013-06-01 In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4 Higuita, Edwin A Jaimes, Fabián A Rugeles, Maria T Montoya, Carlos J AIDS Res Ther Research BACKGROUND: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. METHODS: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. RESULTS: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. CONCLUSIONS: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains. BioMed Central 2013-05-01 /pmc/articles/PMC3668251/ /pubmed/23634877 http://dx.doi.org/10.1186/1742-6405-10-10 Text en Copyright © 2013 Higuita et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Higuita, Edwin A
Jaimes, Fabián A
Rugeles, Maria T
Montoya, Carlos J
In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title_full In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title_fullStr In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title_full_unstemmed In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title_short In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4
title_sort in vivo effect of statins on the expression of the hiv co-receptors ccr5 and cxcr4
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668251/
https://www.ncbi.nlm.nih.gov/pubmed/23634877
http://dx.doi.org/10.1186/1742-6405-10-10
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