Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol
| Autor: | Youjia Cao, Ying Liu, Yajun Duan, Ye Zhang, Yuanli Chen, Miao Yu, Xiaoju Li, Xiaoxiao Yang, Jian Liu, Jihong Han, Zhuo Wei, Xingzhe Ma, Chuanrui Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine viruses Blotting Western Cell Herpesvirus 1 Human QD415-436 Real-Time Polymerase Chain Reaction medicine.disease_cause Biochemistry Interferon-gamma Mice 03 medical and health sciences chemistry.chemical_compound Endocrinology Interferon medicine Animals Humans CRISPR Liver X receptor 25-hydroxycholesterol-3-sulfate Research Articles Liver X Receptors Mice Inbred BALB C interferon γ Cholesterol Hep G2 Cells Cell Biology Metabolism cholesterol 25-hydroxylase Hydroxycholesterols Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Herpes simplex virus chemistry Hepg2 cells Cancer research lipids (amino acids peptides and proteins) CRISPR-Cas Systems Sulfotransferases medicine.drug |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 12, Pp 2287-2296 (2018) |
| ISSN: | 0022-2275 |
| Popis: | 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 LXRα, LXRβ, 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)-γ 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-γ, 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-γ, and 25HC metabolism. |
| Databáze: | OpenAIRE |
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