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

• Published in: Biochemical and biophysical research communications Vol. 419; no. 1; pp. 95 - 98
• Main Authors: Dubrovsky, Larisa, Duyne, Rachel Van, Senina, Svetlana, Guendel, Irene, Pushkarsky, Tatiana, Sviridov, Dmitri, Kashanchi, Fatah, Bukrinsky, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.03.2012
• Subjects: agonists; animal models; Animals; Anticholesteremic Agents - pharmacology; Atherosclerosis; cell transplantation; Disease Models, Animal; high density lipoprotein; HIV infections; HIV Infections - blood; HIV Infections - virology; HIV-1; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus 1; Humanized mice; Humans; Hydrocarbons, Fluorinated - pharmacology; hyperlipidemia; Lipid Metabolism - drug effects; Lipoproteins, HDL - blood; liver; Liver X receptor agonist; Liver X Receptors; metabolism; Mice; Orphan Nuclear Receptors - agonists; Pathogenesis; risk; Stem Cell Transplantation; stem cells; Sulfonamides - pharmacology; virus replication; Virus Replication - drug effects; HIV-1; Humanized mice; Pathogenesis; Liver X receptor agonist; Atherosclerosis
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2012.01.137

► The first demonstration that the effect of HIV infection on HDL can be reproduced in a humanized mouse model of HIV infection. ► Demonstration of anti-HIV activity of LXR agonist in an NSG mouse model of HIV infection. ► Demonstration of protective effect of LXR agonist against HIV-induced reduction of HDL levels in blood. ► Supportive evidence for the indirect mechanism of HIV-induced HDL impairment through the release of a soluble factor. 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-PrkdcscidIL2rgtm1Wjl/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.