Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol
Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol
复制标题
肝脏 X 受体的激活在 25-羟基胆固醇的抗病毒作用中发挥着核心作用。
DOI：
10.1194/jlr.m084558
复制
发表时间：
2018-12-01
影响因子：
6.5
通讯作者：
Duan, Yajun
中科院分区：
文献类型：
--
作者：
Liu, Ying;Wei, Zhuo;Duan, Yajun
Production of 25-hydroxycholesterol (25HC), a potent inhibitor of viral infection, is catalyzed by cholesterol 25-hydroxylase (CH25H). We previously reported that 25HC induced CH25H expression in a liver X receptor (LXR)-dependent manner, implying that LXR can play an important role in antiviral infection. In this study, we determined that activation of LXR by 25HC or synthetic ligands [T0901317 (T317) or GW3965] inhibited infection of herpes simplex virus type 1 (HSV-1) or MLV-(VSV)-GFP in HepG2 cells or RAW 264.7 macrophages. Genetic deletion of LXR alpha, LXR beta, or CH25H expression in HepG2 cells by CRISPR/Cas9 method increased cell susceptibility to HSV-1 infection and attenuated the inhibition of LXR on viral infection. Lack of interferon (IFN)- expression also increased cell susceptibility to viral infection. However, it attenuated, but did not block, the inhibition of LXR on HSV-1 infection. In addition, expression of CH25H, but not IFN-gamma, was inversely correlated to cell susceptibility to viral infection and the antiviral actions of LXR. Metabolism of 25HC into 25HC-3-sulfate (25HC3S) by cholesterol sulfotransferase-2B1b moderately reduced the antiviral actions of 25HC because 25HC3S is a weaker inhibitor of HSV-1 infection than 25HC. Furthermore, administration of T317 to BALB/c mice reduced HSV-1 growth in mouse tissues. Taken together, we demonstrate an antiviral system of 25HC with involvement of LXR activation, interaction between CH25H and IFN-gamma, and 25HC metabolism.
