Liver X receptor agonist inhibits HIV-1 replication and prevents HIV-induced reduction of plasma HDL in humanized mouse model of HIV infection

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• 作者：Larisa Dubrovsky^a ; Rachel Van Duyne^a ; ^b ; Svetlana Senina^b ; Irene Guendel^b ; Tatiana Pushkarsky^a ; Dmitri Sviridov^c ; Fatah Kashanchi^b ; Michael Bukrinsky^a ; ^{mbukrins@email.gwu.edu}
• 关键词：HIV-1 ; Humanized mice ; Atherosclerosis ; Pathogenesis ; Liver X receptor agonist
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：2 March, 2012
• 卷：419
• 期：1
• 页码：95-98
• 文件大小：212 K

摘要

HIV-infected subjects are at high risk of developing atherosclerosis, in part due to virus-induced impairment of HDL metabolism. Here, using as a model of HIV infection the NOD.Cg-Prkdc^scidIL2rg^tm1Wjl/SzJ (NSG) mice humanized by human stem cell transplantation, we demonstrate that LXR agonist TO901317 potently reduces viral replication and prevents HIV-induced reduction of plasma HDL. These results establish that humanized mice can be used to investigate the mechanisms of HIV-induced impairment of HDL formation, a major feature of dyslipidemia associated with HIV-1 infection, and show potential benefits of developing LXR agonists for treatment of HIV-associated cardio-vascular disease.