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. 2012 Mar 2;419(1):95-8.
doi: 10.1016/j.bbrc.2012.01.137. Epub 2012 Feb 4.

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

Larisa Dubrovsky  1 , Rachel Van Duyne, Svetlana Senina, Irene Guendel, Tatiana Pushkarsky, Dmitri Sviridov, Fatah Kashanchi, Michael Bukrinsky
Affiliations

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

Larisa Dubrovsky et al. Biochem Biophys Res Commun. .

Abstract

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(scid)IL2rg(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.

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Figures

Figure 1
Figure 1. Analysis of viral replication in humanized NSG mice
Ten NSG mice were infected with HIV-1 89.6 as described in the text. Two were left untreated (control), 2 were treated with T20 and 4 treated with TO901317 for 2 weeks starting at the time of infection, 2 were treated with T20 and 2 treated with TO901317 for 1 week starting 2 weeks after infection. Virus replication was analyzed 2 weeks (animals treated for 2 weeks) or 3 weeks after infection (animals treated for 1 week) by measuring RT activity (A) or viral load (B) in the plasma.
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References

    1. Asztalos BF, Mujawar Z, Morrow MP, Grant A, Pushkarsky T, Wanke C, Shannon R, Geyer M, Kirchhoff F, Sviridov D, Fitzgerald ML, Bukrinsky M, Mansfield KG. Circulating Nef induces dyslipidemia in simian immunodeficiency virus-infected macaques by suppressing cholesterol efflux. J Infect Dis. 2010;202:614–623. - PMC - PubMed
    1. Crowe SM, Westhorpe CL, Mukhamedova N, Jaworowski A, Sviridov D, Bukrinsky M. The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol. 2010;87:589–598. - PMC - PubMed
    1. Mujawar Z, Rose H, Morrow MP, Pushkarsky T, Dubrovsky L, Mukhamedova N, Fu Y, Dart A, Orenstein JM, Bobryshev YV, Bukrinsky M, Sviridov D. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 2006;4:e365. - PMC - PubMed
    1. Peet DJ, Janowski BA, Mangelsdorf DJ. The LXRs: a new class of oxysterol receptors. Curr Opin Genet Dev. 1998;8:571–575. - PubMed
    1. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol. 2000;16:459–481. - PubMed

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