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

Gene Therapy volume 17, pages 1253–1261 (2010)Cite this article

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Abstract

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 study, 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 seems 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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Acknowledgements

This study financially supported by funds from National Heart Lung Blood Institute/NIH RO1 award, RO1 HL70273-01 and by a Grant-in-Aid from the American Heart Association.

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Authors and Affiliations

  1. Center for Lung Biology, University of South Alabama School of Medicine, Mobile, AL, USA

    V Solodushko & B Fouty

  2. Department of Pharmacology, University of South Alabama School of Medicine, Mobile, AL, USA

    V Solodushko & B Fouty

  3. Department of Internal Medicine, University of South Alabama School of Medicine, Mobile, AL, USA

    B Fouty

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  1. V Solodushko
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  2. B Fouty
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Correspondence to V Solodushko.

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Solodushko, V., Fouty, B. Mifepristone increases gamma-retroviral infection efficiency by enhancing the integration of virus into the genome of infected cells. Gene Ther 17, 1253–1261 (2010). https://doi.org/10.1038/gt.2010.80

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