Institute of Molecular Biosciences, Mahidol University, Salaya, Thailand.
Virology and Cell Technology Research Team, National Center of Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand.
PLoS One. 2023 Oct 17;18(10):e0293010. doi: 10.1371/journal.pone.0293010. eCollection 2023.
Vitamin D has been shown to have antiviral activity in a number of different systems. However, few studies have investigated whether the antiviral activity is exerted through the vitamin D receptor (VDR). In this study, we investigated whether the antiviral activity of a vitamin D receptor agonist (EB1089) towards dengue virus (DENV) was modulated by VDR. To undertake this, VDR was successively overexpressed, knocked down and retargeted through mutation of the nuclear localization signal. In no case was an effect seen on the level of the antiviral activity induced by EB1089, strongly indicating that the antiviral activity of EB1089 is not exerted through VDR. To further explore the antiviral activity of EB1089 in a more biologically relevant system, human neural progenitor cells were differentiated from induced pluripotent stem cells, and infected with Zika virus (ZIKV). EB1089 exerted a significant antiviral effect, reducing virus titers by some 2Log10. In support of the results seen with DENV, no expression of VDR at the protein level was observed. Collectively, these results show that the vitamin D receptor agonist EB1089 exerts its antiviral activity independently of VDR.
维生素 D 已在多种不同系统中表现出抗病毒活性。然而，很少有研究调查这种抗病毒活性是否通过维生素 D 受体 (VDR) 发挥作用。在这项研究中，我们研究了维生素 D 受体激动剂 (EB1089) 对登革热病毒 (DENV) 的抗病毒活性是否受 VDR 调节。为此，通过核定位信号的突变，成功地过表达、敲低和重新靶向 VDR。在任何情况下，EB1089 诱导的抗病毒活性水平均未受到影响，这强烈表明 EB1089 的抗病毒活性不是通过 VDR 发挥作用的。为了在更具生物学相关性的系统中进一步探索 EB1089 的抗病毒活性，从诱导多能干细胞分化出人类神经祖细胞，并感染寨卡病毒 (ZIKV)。EB1089 发挥了显著的抗病毒作用，使病毒滴度降低了约 2Log10。与 DENV 观察到的结果一致，未观察到 VDR 在蛋白质水平上的表达。总之，这些结果表明维生素 D 受体激动剂 EB1089 独立于 VDR 发挥其抗病毒活性。
