Mifepristone increases gamma-retroviral infection efficiency by enhancing the integration of virus into the genome of infected cells.
Mifepristone increases gamma-retroviral infection efficiency by enhancing the integration of virus into the genome of infected cells.
复制标题
米非司酮通过增强病毒与受感染细胞基因组的整合来提高 γ-逆转录病毒感染效率。
作者：
Solodushko,V;Fouty,B
γ-逆转录病毒通常用于将基因递送到细胞。以前，我们证明了合成的抗糖皮质激素和抗孕激素剂，米非司酮，在不同的靶细胞中增加γ-逆转录病毒感染效率，独立于病毒滴度。在这项研究中，我们将研究这种情况是如何发生的。我们研究了米非司酮对病毒感染的不同步骤（病毒进入，病毒存活，病毒DNA合成和逆转录病毒整合到宿主基因组中）在三个不同的逆转录病毒骨架中使用不同的病毒识别受体的影响。我们还测试了糖皮质激素和孕激素受体在介导米非司酮增加γ-逆转录病毒感染能力中的潜在作用。我们发现，米非司酮增加γ-逆转录病毒感染的效率，通过促进病毒整合到宿主基因组中，这种效果似乎是由于米非司酮的抗糖皮质激素，但不是其抗β-内酰胺酶，活性。这些结果表明，糖皮质激素受体的抑制增强了逆转录病毒整合到宿主基因组中，并表明细胞可能对逆转录病毒感染具有天然保护作用，糖皮质激素受体拮抗剂可以降低这种保护作用。
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.