title: 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 transfectedin vivowith 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 responsesin vivo. 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.
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Shengchang
authors.initials: S
authors.lastname: Deng
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangxi Police College, Nanchang, Jiangxi 330103, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ouyang
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Junping
authors.initials: J
authors.lastname: Xiong
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Tu
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Keping
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Third People's Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
authors.forename: Zengliang
authors.initials: Z
authors.lastname: Song
authors.affiliation: School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Zhang
keywords: dexamethsone; glucocorticoid receptor; importin α; lentiviral vector; mouse