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Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells

Gamma-retroviruses are commonly used to deliver genes to cells. Previously we demonstrated that the synthetic anti-glucocorticoid and anti-progestin agent, mifepristone, increased gamma-retroviral infection efficiency in different target cells, independent of viral titer. In this paper, we examine h...

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Detalles Bibliográficos
Autores principales: Solodushko, Victor, Fouty, Brian
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927725/
https://www.ncbi.nlm.nih.gov/pubmed/20485384
http://dx.doi.org/10.1038/gt.2010.80
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author Solodushko, Victor
Fouty, Brian
author_facet Solodushko, Victor
Fouty, Brian
author_sort Solodushko, Victor
collection PubMed
description Gamma-retroviruses are commonly used to deliver genes to cells. Previously we demonstrated that the synthetic anti-glucocorticoid and anti-progestin agent, mifepristone, increased gamma-retroviral infection efficiency in different target cells, independent of viral titer. In this paper, we examine how this occurs. We studied the effect of mifepristone on different steps of viral infection (viral entry, viral survival, viral DNA synthesis and retrovirus integration into the host genome) in three distinct retroviral backbones using different virus recognition receptors. We also tested the potential role of glucocorticoid and progesterone receptors in mediating mifepristone’s ability to increase gamma-retroviral infectivity. We show that mifepristone increases gamma-retroviral infection efficiency by facilitating viral integration into the host genome and that this effect appears to be due to mifepristone’s anti-glucocorticoid, but not its anti-progestin, activity. These results suggest that inhibition of the glucocorticoid receptor enhances retroviral integration into the host genome and indicates that cells may have a natural protection again retroviral infection that may be reduced by glucocorticoid receptor antagonists.
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spelling pubmed-29277252011-04-01 Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells Solodushko, Victor Fouty, Brian Gene Ther Article Gamma-retroviruses are commonly used to deliver genes to cells. Previously we demonstrated that the synthetic anti-glucocorticoid and anti-progestin agent, mifepristone, increased gamma-retroviral infection efficiency in different target cells, independent of viral titer. In this paper, we examine how this occurs. We studied the effect of mifepristone on different steps of viral infection (viral entry, viral survival, viral DNA synthesis and retrovirus integration into the host genome) in three distinct retroviral backbones using different virus recognition receptors. We also tested the potential role of glucocorticoid and progesterone receptors in mediating mifepristone’s ability to increase gamma-retroviral infectivity. We show that mifepristone increases gamma-retroviral infection efficiency by facilitating viral integration into the host genome and that this effect appears to be due to mifepristone’s anti-glucocorticoid, but not its anti-progestin, activity. These results suggest that inhibition of the glucocorticoid receptor enhances retroviral integration into the host genome and indicates that cells may have a natural protection again retroviral infection that may be reduced by glucocorticoid receptor antagonists. 2010-05-20 2010-10 /pmc/articles/PMC2927725/ /pubmed/20485384 http://dx.doi.org/10.1038/gt.2010.80 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Solodushko, Victor
Fouty, Brian
Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title_full Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title_fullStr Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title_full_unstemmed Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title_short Mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
title_sort mifepristone increases gamma-retroviral infection efficiency by enhancing integration of virus into the genome of infected cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927725/
https://www.ncbi.nlm.nih.gov/pubmed/20485384
http://dx.doi.org/10.1038/gt.2010.80
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