The effect of dexamethasone on lentiviral vector infection is associated with importin α

Abstract

Importin α (Imα) plays an important role during the shuttling of the HIV-1 preintegration complex (PIC) from the cytoplasm to the nucleus. Imα may bind to the glucocorticoid receptor (GR), which is localized to nucleus following hormone binding. However, it remains unclear whether the binding of dexamethasone (Dex) to GR affects the Imα redistribution and, thus, alters PIC import. In our study, 293T cells were transfected with the lentiviral vector (LV) carrying the luciferase (Luci) gene following Dex or RU486 pretreatment. The Luci activity (LucA) in the Dex or RU486 group was significantly higher compared to that in the control group (P≤0.01). The effects of Dex and RU486 were inhibited by the Imα inhibitor Bimax1 (P≤0.01), although the inhibitory effect of Bimax1 was alleviated by increasing the Dex dose. Furthermore, it was observed that the LucA in the 30-min Dex treatment group was lower compared to that in the 30-min Dex pretreatment group (P≤0.01). These results suggested that Dex may improve PIC import via increasing the cytoplasmic Imα levels. Kunming mice were transfected with the LV, either 30 min or 15 h following an intraperitoneal injection of Dex. The LucA in the liver of the 30-min group mice was significantly lower compared to that of the 15-h group mice (P≤0.01), suggesting that the effect of Dex on LV infection depends mainly on the suppression of immune and inflammatory responses. Taken together, our data indicated that the effect of Dex on LV infection may be associated with Imα, constituting a novel signaling pathway mediating the effects of Dex on HIV-1 infection.

A straightforward microfluidic-based approach toward optimizing transduction efficiency of HIV-1-derived lentiviral vectors in BCP-ALL cells

“…Many approaches have been taken into account to enhance LV transduction efficiency, including polycations (e.g., polybrene and protamine sulfate) [9] , spinoculation [10] , Retronectin [11] , and some adjuvants (e.g., Rapamycin [12] , Dexamethasone [13] , BX795 [14] , Cyclosporine A and H [15] , Staurosporine [16] , phorbol 12-myristate13-acetate (PMA) [17] , prostaglandin E2 and Poloxamer 407 [18] ). The abovementioned approaches have been used in standard transduction systems, such as well-plates and flasks.…”